Search results for: biodegradable micelles

Authors: Sophio Kobauri, Vladimir P. Torchilin, David Tugushi, Ramaz Katsarava

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Nanotherapy is an actual newest mode of treatment numerous diseases using nanoparticles (NPs) loading with different pharmaceuticals. NPs of biodegradable polymeric micelles (PMs) are gaining increased attention for their numerous and attractive abilities to be used in a variety of applications in the various fields of medicine. The present paper deals with the synthesis of a class of biodegradable micelle-forming polymers, namely ABA triblock-copolymer in which A-blocks represent amino-poly(ethylene glycol) (H₂N-PEG) and B-block is biodegradable amino acid-based poly(ester amide) constituted of α-amino acid – L-phenylalanine. The obtained copolymer formed micelles of 70±4 nm size at 10 mg/mL concentration.

Keywords: amino acids, biodegradable poly (ester amide), amphiphilic triblock-copolymer, micelles

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Authors: Sophio Kobauri, David Tugushi, Vladimir P. Torchilin, Ramaz Katsarava

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Hydrophobic / hydrophilically modified functional polymers are of high interest in modern biomedicine due to their ability to solubilize water-insoluble / poorly soluble (hydrophobic) drugs. Among the many approaches that are being developed in this direction, one of the most effective methods is the use of polymeric micelles (PMs) (micelles formed by amphiphilic block-copolymers) for solubilization of hydrophobic biologicals. For therapeutic purposes, PMs are required to be stable and biodegradable, although quite a few amphiphilic block-copolymers are described capable of forming stable micelles with good solubilization properties. For obtaining micelle-forming block-copolymers, polyethylene glycol (PEG) derivatives are desirable to use as hydrophilic shell because it represents the most popular biocompatible hydrophilic block and various hydrophobic blocks (polymers) can be attached to it. Although the construction of the hydrophobic core, due to the complex requirements and micelles structure development, is the very actual and the main problem for nanobioengineers. Considering the above, our research goal was obtaining biodegradable micelles for the solubilization of hydrophobic drugs and biologicals. For this purpose, we used biodegradable polymers– pseudo-proteins (PPs)(synthesized with naturally occurring amino acids and other non-toxic building blocks, such as fatty diols and dicarboxylic acids) as hydrophobic core since these polymers showed reasonable biodegradation rates and excellent biocompatibility. In the present study, we used the hydrophobic amino acid – L-phenylalanine (MW 4000-8000Da) instead of L-leucine. Amino-PEG (MW 2000Da) was used as hydrophilic fragments for constructing the suitable micelles. The molecular weight of PP (the hydrophobic core of micelle) was regulated by variation of used monomers ratios. Micelles were obtained by dissolving of synthesized amphiphilic polymer in water. The micelle-forming property was tested using dynamic light scattering (Malvern zetasizer NanoZSZEN3600). The study showed that obtaining amphiphilic block-copolymer form stable neutral micelles 100 ± 7 nm in size at 10mg/mL concentration, which is considered as an optimal range for pharmaceutical micelles. The obtained preliminary data allow us to conclude that the obtained micelles are suitable for the delivery of poorly water-soluble drugs and biologicals.

Keywords: amino acid – L-phenylalanine, pseudo-proteins, amphiphilic block-copolymers, biodegradable micelles

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Authors: Salma E. Ahmed

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Since the mid 50’s, enormous attention has been paid towards nanocarriers and their applications in drug and gene delivery. Among these vesicles, liposomes and micelles have been heavily investigated due to their many advantages over other types. Liposomes, for instance, are mostly distinguished by their ability to encapsulate hydrophobic, hydrophilic and amphiphilic drugs. Micelles, on the other hand, are self-assembled shells of lipids, amphiphilic or oppositely charged block copolymers that, once exposed to aqueous media, can entrap hydrophobic agents, and possess prolonged circulation in the bloodstream. Both carriers are considered compatible and biodegradable. Nevertheless, they have limited stabilities, chemical versatilities, and drug encapsulation efficiencies. In order to overcome these downsides, strategies for optimizing a novel drug delivery system that has the architecture of liposomes and polymeric characteristics of micelles have been evolved. Polymersomes are vehicles with fluidic cores and hydrophobic shells that are protected and isolated from the aqueous media by the hydrated hydrophilic brushes which give the carrier its distinctive polymeric bilayer shape. Similar to liposomes, this merit enables the carrier to encapsulate a wide range of agents, despite their affinities and solubilities in water. Adding to this, the high molecular weight of the amphiphiles that build the body of the polymersomes increases their colloidal and chemical stabilities and reduces the permeability of the polymeric membranes, which makes the vesicles more protective to the encapsulated drug. These carriers can also be modified in ways that make them responsive when targeted or triggered, by manipulating their composition and attaching moieties and conjugates to the body of the carriers. These appealing characteristics, in addition to the ease of synthesis, gave the polymersomes greater potentials in the area of drug delivery. Thus, their design and characterization, in comparison with liposomes and micelles, are briefly reviewed in this work.

Keywords: controlled release, liposomes, micelles, polymersomes, targeting

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Vijaykumar Patel, P. Bahadur

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Microstructural evolution of a cationic gemini surfactant 12-4-12 micelles in the presence of bile salts has been investigated using different techniques. A negative value of interaction parameter evaluated from surface tension measurements is a signature of strong synergistic interaction between oppositely charged surfactants. Both the bile salts compete with each other in inducing the micellar transition of 12-4-12 micelles depending on their hydrophobicity. Viscosity measurements disclose that loading of bile salts induces morphological changes in 12-4-12 micelles; sodium deoxycholate is more efficient in altering the aggregation behaviour of 12-4-12 micelles compared to sodium cholate and presents pronounced increase in viscosity and micellar growth which is suppressed at elevated temperatures. A remarkable growth of 12-4-12 micelles in the presence of sodium deoxycholate at low pH has been ascribed to the solubilization of bile acids formed in acidic medium. Small angle neutron scattering experiments provided size and shape of 12-4-12/bile salt mixed micelles are explicated on the basis of hydrophobicity of bile salts. The location of bile salts in micelle was determined from nuclear overhauser effect spectroscopy. The present study characterizes 12-4-12 gemini-bile salt mixed systems which significantly enriches our knowledge, and such a structural transition provides an opportunity to use these bioamphiphiles as delivery vehicles and in some pharmaceutical formulations.

Keywords: gemini surfactants, bile salts, SANS (small angle neutron scattering), NOESY (nuclear overhauser effect spectroscopy)

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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Authors: Dong Tang, Yongli Zhao

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The study of the microstructure of asphalt is of great importance for the analysis of its macroscopic properties. However, the peculiarities of the chemical composition of the asphalt itself and the limitations of existing direct imaging techniques have caused researchers to face many obstacles in studying the microstructure of asphalt. The advantage of small-angle X-ray scattering (SAXS) is that it allows quantitative determination of the internal structure of opaque materials and is suitable for analyzing the microstructure of materials. Therefore, the SAXS technique was used to study the evolution of microstructures on the nanoscale during asphalt aging. And the reasons for the change in scattering contrast during asphalt aging were also explained with the help of Fourier transform infrared spectroscopy (FTIR). SAXS experimental results show that the SAXS curves of asphalt are similar to the scattering curves of scattering objects with two-level structures. The Porod curve for asphalt shows that there is no obvious interface between the micelles and the surrounding mediums, and there is only a fluctuation of the hot electron density between the two. The Beaucage model fit SAXS patterns shows that the scattering coefficient P of the asphaltene clusters as well as the size of the micelles, gradually increase with the aging of the asphalt. Furthermore, aggregation exists between the micelles of asphalt and becomes more pronounced with increasing aging. During asphalt aging, the electron density difference between the micelles and the surrounding mediums gradually increases, leading to an increase in the scattering contrast of the asphalt. Under long-term aging conditions due to the gradual transition from maltenes to asphaltenes, the electron density difference between the micelles and the surrounding mediums decreases, resulting in a decrease in the scattering contrast of asphalt SAXS. Finally, this paper correlates the macroscopic properties of asphalt with microstructural parameters, and the results show that the high-temperature rutting resistance of asphalt is enhanced and the low-temperature cracking resistance decreases due to the aggregation of micelles and the generation of new micelles. These results are useful for understanding the relationship between changes in microstructure and changes in properties during asphalt aging and provide theoretical guidance for the regeneration of aged asphalt.

Keywords: asphalt, Beaucage model, microstructure, SAXS

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Authors: S. Pal, R. Singh, S. Sivakumar, D. Kunzru

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AOT stabilized reverse micelles of deionized water, dispersed in isooctane have been used to synthesize bimetallic nickel tungsten nanoparticles. Prepared nanoparticles were supported on γ-Al2O3 followed by calcination at 500oC. Characterizations of the nanoparticles were done by TEM, XRD, FTIR, XRF, TGA and BET. XRF results showed that this method gave good composition control with W/Ni weight ratio equal to 3.2. TEM images showed particle size of 5-10 nm. Removal of surfactant after calcination was confirmed by TGA and FTIR.

Keywords: nanoparticles, reverse micelles, nickel, tungsten

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Authors: Tej Varma Y, Debi D. Pant

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Photophysics and rotational dynamics of the fluorescent probe, 6-methoxyquinoline (6MQ) with cationic surfactant, alkyltrimethylammonium bromide (nTAB) micelle solutions have been investigated (n = 12, 14 and 16). Absorption and emission peaks of the dye have been observed to shift at concentrations around critical micellar concentration (cmc) of nTAB compared to that of bulk solutions suggesting probe is in a lower polar environment. The probe senses changes in polarity (ET (30)) brought about by variation of surfactant chain length concentration and is invariably solubilized in the aqueous interface or palisade layer. The order of change in polarity observed was DTAB > CTAB > TTAB. The binding constant study shows that the probe binds strongest with TTAB (is of the order TTAB > CTAB > DTAB) due to deeper penetration into the micelle. The anisotropy decay for the probe in all the nTAB micelles studied have been rationalized based on a two-step model consisting of fast-restricted rotation of the probe and slow lateral diffusion of the probe in the micelle that is coupled to the overall rotation of the micelle. Fluorescence lifetime measurements of probe in the cationic micelles demonstrate the close proximity of the 6MQ to the Br - counterions. The fluorescence lifetimes of TTAB and DTAB are much shorter than in CTAB. These results indicate that 6MQ resides to a substantial degree in the head group region of the micelles. All the changes observed in the steady state fluorescence, microenvironment, fluorescence lifetimes, fluorescence anisotropy, and other calculations are in agreement with each other suggesting binding of the cationic surfactant with the neutral dye molecule.

Keywords: photophysics, chain length, ntaB, micelles

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Authors: Deepak Kakde, Steve Howdle, Derek Irvine, Cameron Alexander

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The poor aqueous solubility is one of the major obstacles in the formulation development of many drugs. Around 70% of drugs are poorly soluble in aqueous media. In the last few decades, micelles have emerged as one of the major tools for solubilization of hydrophobic drugs. Micelles are nanosized structures (10-100nm) obtained by self-assembly of amphiphilic molecules into the water. The hydrophobic part of the micelle forms core which is surrounded by a hydrophilic outer shell called corona. These core-shell structures have been used as a drug delivery vehicle for many years. Although, the utility of micelles have been reduced due to the lack of sustainable materials. In the present study, a novel methoxy poly(ethylene glycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer was synthesized by ring opening polymerization (ROP) of renewable ε-decalactone (ε-DL) monomers on methoxy poly(ethylene glycol) (mPEG) initiator using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a organocatalyst. All the reactions were conducted in bulk to avoid the use of toxic organic solvents. The copolymer was characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC).The mPEG-b-PεDL block copolymeric micelles containing indomethacin (IND) were prepared by nanoprecipitation method and evaluated as drug delivery vehicle. The size of the micelles was less than 40nm with narrow polydispersity pattern. TEM image showed uniform distribution of spherical micelles defined by clear surface boundary. The indomethacin loading was 7.4% for copolymer with molecular weight of 13000 and drug/polymer weight ratio of 4/50. The higher drug/polymer ratio decreased the drug loading. The drug release study in PBS (pH7.4) showed a sustained release of drug over a period of 24hr. In conclusion, we have developed a new sustainable polymeric material for IND delivery by combining the green synthetic approach with the use of renewable monomer for sustainable development of polymeric nanomedicine.

Keywords: dopolymer, ε-decalactone, indomethacin, micelles

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Authors: Herman Ruswan Suwarman, Ahmad Rivai, Mochamad Saidiman, Kuncoro Diharjo, Dody Ariawan

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The use of biodegradable composite to solve ecological and environmental problems has currently risen as a trend. With the increasing use of biodegradable composite comes an increasing need to fabricate it properly. Yet this understanding has remained a challenge for the design engineer. Therefore, this study aims to explore how to combine coconut coir as a reinforcing material and polypropylene (PP) as a biodegradable polymer matrix. By using Hotpress Molding, two methods were developed and compared. The difference between these two methods is not only the step of fabrication but also the raw material. The first method involved a PP sheet and the second used PP pellets directly. Based on the results, it can be concluded that PP pellets yield better results, where the composite was produced in a shorter time, with an evenly distributed coconut coir and a smaller number of voids.

Keywords: biodegradable, coconut coir, hot press molding, polypropylene

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

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The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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Authors: Susmita Roy, Madhavan Nallani

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In recent years' polymersomes, self-assembled polymeric vesicles emerge from block copolymers, have been widely investigated due to their enhance stability and unique advantageous properties compared to their phospholipid counterpart, liposomes, dendrimers, and micelles. It provides a distinctive platform for advanced therapeutics and the creation of complex (bio) catalytically active systems for research in Nanomedicine and synthetic biology. Inspired by nature, where compartmentalization of biological components is all ubiquitous, we are interested in developing a platform technology of self-assembled multifunctional compartments with applications in areas from targeted drug/gene delivery, biosensing, pharmaceutical to cosmetics. Polymersome surfaces can be a proper choice of derivatization with a controlled amount of functional groups. To achieve site-specific targeting of polymersomes, biological recognition motives can be attached to the polymersomes surface by standard bioconjugation techniques, (like esterification, amidation, thiol-maleimide coupling, click-chemistry routes or other coupling methods). Herein, we are developing easy going, one-step bioconjugation strategies for site-specific surface functionalized biodegradable polymeric and/or polymer-lipid hybrid vesicles for targeted drug delivery. Biodegradable polymer, polycaprolactone-b-polyethylene glycol (PCL-PEG), polylactic acid-b-polyethylene glycol (PLA-PEG) and phospholipid, 1-palmitoyl-2- oleoyl-sn-glycero-3-phosphocholine (POPC) has been widely used for numerous vesicle formulations. Some of these drug-loaded formulations are being tested on mice for controlled release. These surface functionalized polymersomes are also appropriate for membrane protein reconstitution/insertion, antibodies conjugation and various bioconjugation with diverse targeted molecules for controlled drug delivery.

Keywords: drug delivery, membrane protein, polymersome, surface modification

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Authors: Zaid Almahmoud, Rana Mahmoud

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To mitigate the environmental impacts of throwing away plastic waste, there has been a recent interest in manufacturing and producing biodegradable plastics. Here, we study a new class of biodegradable plastics which are mixed with external natural additives, including catalytic additives that lead to a successful degradation of the resulting material. To recommend the best alternative among multiple materials, we propose a multi-objective AI model that evaluates the material against multiple objectives given the material properties. As a proof of concept, the AI model was implemented in an expert system and evaluated using multiple materials. Our findings showed that Polyethylene Terephalate is potentially the best biodegradable plastic substitute based on its material properties. Therefore, it is recommended that governments shift the attention to the use of Polyethylene Terephalate in the manufacturing of bottles to gain a great environmental and sustainable benefits.

Keywords: plastic bottles, expert systems, multi-objective model, biodegradable substitutes

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Authors: Abdulrahman Sumayli

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Natural Zinc has many significant biological functions, including developments and sustainable of bones and wound healing. Metallic zinc has recently been explored as potential biomaterials that have preferable biodegradable, biocompatible, and mechanical properties. Pure metal zinc has a preferable physical and mechanical properties for biodegradable and biocompatible applications such as density and modulus of elasticity. The aim of the research is to make different Zn-based metallic alloys and test them effectively to be used as biocompatible and biodegradable materials in the field biomedical application. Microstructure study of the as-cast alloys will be examined using SEM (scanning electron microscope) followed by X-ray diffraction investigated so as to evaluate phase constitution of the designed alloys. After that, immersion test and electrochemical test will be applied to the designed alloys so as to study bio corrosion behaviour of the proposed alloys. Finally, in vitro cytocompatibility well conducted to study biocompatibility of the made alloys.

Keywords: Zn-based alloys, biodegradable and biocompatible materials, cytotoxicity test, neutron synchrotron imaging

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Authors: Abbul B. Khan, Neeraj Dohare, Rajan Patel

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The mixed micellization of adiphenine hydrochloride (ADP) with 1-decyl-3-methylimidazolium chloride (C10mim.Cl), was investigated at different mole fractions and temperatures by surface tension measurements. The synergistic behavior (i.e., non-ideal behavior) for binary mixtures was explained by the deviation of critical micelle concentration (cmc) from ideal critical micelle concentration (cmc*), micellar mole fraction (Xim) from ideal micellar mole fraction (Xiideal), the values of interaction parameter (β) and activity coefficients (fi) (for both mixed micelles and mixed monolayer). The excess free energy (∆Gex) for the ADP- C10mim.Cl binary mixtures explain the stability of mixed micelles in comparison to micelles of pure ADP and C10mim.Cl. Interfacial parameters, i.e., Gibbs surface excess (Гmax), minimum head group area at air/ water interface (Amin), and free energy of micellization (ΔG0m) were also evaluated for the systems.

Keywords: adiphenine hydrochloride, critical micelle concentration, interaction parameter, activity coefficient

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Authors: Siriporn Okonogi, Pimpak Phumat, Sakornrat Khongkhunthian

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Piper betle has been extensively reported for various pharmacological effects including antimicrobial activity. 4-Allylpyrocatechol (AC) is a principle active compound found in P. betle. However, AC has a problem of solubility in water. The aims of the present study were to prepare AC loaded polymeric micelles for enhancing its water solubility and to evaluate its anti-biofilm activity against oral phathogenic bacteria. AC was loaded in polymeric micelles (PM) of Pluronic F127 by using thin film hydration method to obtain AC loaded PM (PMAC). The results revealed that AC in the form of PMAC possessed high water solubility. PMAC particles were characterized using a transmission electron microscope and photon correlation spectroscopy. Determination of entrapment efficiency (EE) and loading capacity (LC) of PMAC was done by using high-performance liquid chromatography. The highest EE (86.33 ± 14.27 %) and LC (19.25 ± 3.18 %) of PMAC were found when the weight ratio of polymer to AC was 4 to 1. At this ratio, the particles showed spherical in shape with the size of 38.83 ± 1.36 nm and polydispersity index of 0.28 ± 0.10. Zeta potential of the particles is negative with the value of 16.43 ± 0.55 mV. Crystal violet assay and confocal microscopy were applied to evaluate the effects of PMAC on Streptococcus mutans biofilms using chlorhexidine (CHX) as a positive control. PMAC contained 1.5 mg/mL AC could potentially inhibit (102.01 ± 9.18%) and significantly eradicate (85.05 ± 2.03 %) these biofilms (p < 0.05). Comparison with CHX, PMAC showed slightly similar biofilm inhibition but significantly stronger biofilm eradication (p < 0.05) than CHX. It is concluded that PMAC can enhance water solubility and anti-biofilm activity of AC.

Keywords: pluronic, polymeric micelles, solubility, 4-allylpyrocathecol, Streptococcus mutans, anti-biofilm

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Authors: Alaa Hamed Salama, Rehab Nabil Shamma

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Introduction: Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim of this study was to review the aqueous-based formulation of drug-loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly (ethylene oxide)-poly (propylene oxide) for the more effective encapsulation of Lornoxicam (LX) as a hydrophobic model drug. Methods: The co-micellization process of 10% binary systems combining different weight ratios of the highly hydrophilic poloxamers; Synperonic® PE/P84, and Synperonic® PE/F127 and the hydrophobic poloxamine counterpart (Tetronic® T701) was investigated by means of photon correlation spectroscopy and cloud point. The drug-loaded micelles were tested for their solubilizing capacity towards LX. Results: Results showed a sharp solubility increase from 0.46 mg/ml up to more than 4.34 mg/ml, representing about 136-fold increase. Optimized formulation was selected to achieve maximum drug solubilizing power and clarity with lowest possible particle size. The optimized formulation was characterized by 1HNMR analysis which revealed complete encapsulation of the drug within the micelles. Further investigations by histopathological and confocal laser studies revealed the non-irritant nature and good corneal penetrating power of the proposed nano-formulation. Conclusion: LX-loaded polymeric nanomicellar formulation was fabricated allowing easy application of the drug in the form of clear eye drops that do not cause blurred vision or discomfort, thus achieving high patient compliance.

Keywords: confocal laser scanning microscopy, Histopathological studies, Lornoxicam, micellar solubilization

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Authors: Mahsa Fathollahzadeh

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The various nanoparticles employed in drug delivery applications include micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, and nanotubes. Micelles, composed of amphiphilic block copolymers, can encapsulate hydrophobic molecules, allowing for targeted delivery. Liposomes, vesicular structures made up of phospholipids, can encapsulate both hydrophobic and hydrophilic molecules, providing a flexible platform for delivering therapeutic agents. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are designed to improve the stability and bioavailability of lipophilic drugs. Polymeric nanoparticles, such as poly(lactic-co-glycolic acid) (PLGA), are biodegradable and can be engineered to release drugs in a controlled manner. Functionalized nanoparticles, coated with targeting ligands or antibodies, can specifically target diseased cells or tissues. Nanocrystals, engineered to have specific surface properties, can enhance the solubility and bioavailability of poorly soluble drugs. Cyclodextrins, doughnut-shaped molecules with hydrophobic cavities, can be complex with hydrophobic molecules, allowing for improved solubility and bioavailability. Dendrimers, branched polymers with a central core, can be designed to deliver multiple therapeutic agents simultaneously. Nanotubes and metallic nanoparticles, such as gold nanoparticles, offer real-time tracking capabilities and can be used to detect biomolecular interactions. The use of these nanoparticles has revolutionized the field of drug delivery, enabling targeted and controlled release of therapeutic agents, reduced toxicity, and improved patient outcomes.

Keywords: nanotechnology, nanopharmaceuticals, drug-delivery, proteins, ligands, nanoparticles, chemistry

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

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Authors: Andres M. Tuates Jr., Ofero A. Caparino

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Plastics have achieved a dominant position in agriculture because of their transparency, lightness in weight, impermeability to water and their resistance to microbial attack. However, this generates a higher quantity of wastes that are difficult to dispose of by farmers. To address these problems, the project aim to develop and evaluate the biodegradable film for mango fruit bag during development. The PBS and starch were melt-blended in a twin-screw extruder and then blown into film extrusion machine. The physic-chemical-mechanical properties of biodegradable fruit bag were done following standard methods of test. Field testing of fruit bag was also conducted to evaluate its durability and efficiency field condition. The PHilMech-FiC fruit bag is made of biodegradable material measuring 6 x 8 inches with a thickness of 150 microns. The tensile strength is within the range of LDPE while the elongation is within the range of HDPE. It is projected that after thirty-six (36) weeks, the film will be totally degraded. Results of field testing show that the quality of harvested fruits using PHilMech-FiC biodegradable fruit bag in terms of percent marketable, non-marketable and export, peel color at the ripe stage, flesh color, TSS, oBrix, percent edible portion is comparable with the existing bagging materials such as Chinese brown paper bag and old newspaper.

Keywords: cassava starch, PBS, biodegradable, chemical, mechanical properties

Procedia PDF Downloads 278

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

Procedia PDF Downloads 310

Authors: V. Villa-Cruz, H. Pérez-Ladron de Guevara, J. E. Diaz-Díaz

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Static Light Scattering (SLS) was used as a method to analyse cow's milk raw, coming from the town of Lagos de Moreno, Jalisco, Mexico. This method is based on the analysis of the dispersion of light laser produced by a set of particles in solution. Based on the above, raw milk, which contains particles of fat globules, with a diameter of 2000 nm and particles of micelles of protein with 300 nm in diameter were analyzed. For this, dilutions of commercial milk were made (1.0%, 2.0% and 3.3%) to obtain a pattern of laser light scattering and also made measurements of raw cow's milk. Readings were taken in a sweep initial angle 10° to 170°, results were analyzed with the program OriginPro 7. The SLS method gives us an estimate of the percentage of fat content in milk samples. It can be concluded that the SLS method, is a quick method of analysis to detect adulteration in raw cow's milk.

Keywords: light scattering, milk analysis, adulteration in milk, micelles, OriginPro

Procedia PDF Downloads 375

Authors: Minjung Park, Jimin Park, Youngwoon Kim, Hyungseop Han, Myoungryul Ok, Hojeong Jeon, Hyunkwang Seok, Yuchan Kim

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Magnesium is an essential element in human body and has unique characteristics such as bioabsorbable and biodegradable properties. Therefore, there has been much attention on studies on the implants based on magnesium to avoid subsequent surgery. However, high amount of hydrogen gas is generated by relatively severe corrosion of magnesium especially in aqueous condition with chloride ions. And it contributes to the causes of swelling of skin and causes consequent inflammation of soft tissue where is directly in contact with implants. Therefore, there is still concern about the safety of the using biodegradable magnesium alloys, which is limited to various applications. In this study, we analyzed the influence of coenzyme on corrosion behavior of magnesium. The analysis of corrosion rate was held by using Hanks’ balanced salt solution (HBSS) as a body stimulated fluid and in condition of 37°C. Thus, with deferring the concentration of the coenzyme used in this study, corrosion rates from 0.0654ml/ cm² to 0.0438ml/cm² were observed in immersion tests. Also, comparable results were obtained in electrochemical tests. Results showed that hydrogen gas produced from corrosion of magnesium can be controlled.

Keywords: biodegradable magnesium, biomaterials, coenzyme, corrosion

Procedia PDF Downloads 422

Authors: Abdulrahman T. Essa, Ahmed Aied, Omar Hamid, Felicity R. A. J. Rose, Kevin M. Shakesheff

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Biodegradable poly(ester amide)s are promising polymers for biomedical applications such as drug delivery and tissue engineering because of their optimized chemical and physical properties. In this study, we developed a biodegradable polyester amide elastomer poly(serinol sebacate) (PSS) composed of crosslinked networks based on serinol and sebacic acid. The synthesized polymers were characterized to evaluate their chemical structures, mechanical properties, degradation behaviors and in vitro cytocompatibility. Analysis of proton nuclear magnetic resonance and Fourier transform infrared spectroscopy revealed the structure of the polymer. The PSS exhibit excellent solubility in a variety of solvents such as methanol, dimethyl sulfoxide and dimethylformamide. More importantly, the mechanical properties of PSS could be tuned by changing the curing conditions. In addition, the 3T3 fibroblast cells cultured on the PSS demonstrated good cell attachment and high viability.

Keywords: biodegradable, biomaterial, elastomer, mechanical properties, poly(serinol sebacate)

Procedia PDF Downloads 354

Authors: Marylene S. Eder, Dorothy M. Jao, Paolo Marc Nicolas S. Laspiñas, Pukilan A. Malim, Sarah Jean D. Raterta

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Trash Dash is an android game application developed to serve as an alternative tool to practice proper waste segregation for children ages 3 years old and above. The researchers designed the application using Unity 3D and developed the text file that served as the database of the game application. An observation of a pre-school teacher shows that children know how to throw their garbage but they do not know yet how to segregate wastes. After launching the mobile application to K-2 pupils 4 – 5 years of age, the researchers have noticed that children within this age are active and motivated to learn the difference between biodegradable and non-biodegradable. Based on the result of usability test conducted, it was concluded that the game is easy to use and children will most likely use this application frequently. Furthermore, the children may need assistance from their parents and teachers when playing the game. An actual testing of the application has been conducted to different devices as well as functionality test by Thwack Application and it can be concluded that the mobile application can be launched and installed on a device with a minimum API requirement of Gingerbread (2.3.1).

Keywords: waste segregation, android application, biodegradable, non-biodegradable

Procedia PDF Downloads 445

Authors: Juraj Beniak, Ľubomír Šooš, Peter Križan, Miloš Matúš

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Within Rapid Prototyping technologies are used many types of materials. Many of them are recyclable but there are still as plastic like, so practically they do not degrade in the landfill. Polylactic acid (PLA) is one of the special plastic materials which are biodegradable and also available for 3D printing within Fused Deposition Modelling (FDM) technology. The question is, if the mechanical properties of produced models are comparable to similar technical plastic materials which are usual for prototype production. Presented paper shows the experiments results for tensile strength measurements for specimens prepared with different 3D printer settings and model orientation. Paper contains also the comparison of tensile strength values with values measured on specimens produced by conventional technologies as injection moulding.

Keywords: 3D printing, biodegradable plastic, fused deposition modeling, PLA plastic, rapid prototyping

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Authors: Fernando G. Torres, Omar P. Troncoso

Abstract:

Quercetin is a naturally occurring polyphenol found in many vegetables, such as onion, with antioxidant properties. It is a dietary component with a documented role in reducing different human cancers. However, its low bioavailability, poor water solubility, and chemical instability limit its applications. Different nano-delivery systems such as nanoparticles, micelles, and nanohydrogels have been studied in order to improve the bioavailability of quercetin. Nanoparticles based on natural polymers such as starch have the advantage of being biocompatible, biodegradable, and non-toxic. In this study, quercetin was loaded into starch nanoparticles using a nanoprecipitation method. Different routes, using sodium tripolyphosphate and Tween® 80 as tensioactive agents, were tested in order to obtain an optimized starch-based nano-delivery system. The characterization of the nanoparticles loaded with quercetin was assessed by Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Zeta potential, and Differential scanning calorimetry. UV-vis spectrophotometry was used to evaluate the loading efficiency and capacity of the samples. The results showed that starch-based systems could be successfully used for the nano-delivery of quercetin.

Keywords: starch nanoparticles, nanoprecipitation, quercetin, biomedical applications

Procedia PDF Downloads 140

Authors: Aloke Bapli, Debabrata Seth

Abstract:

Graphene oxide (GO) is the two-dimensional (2D) nanoscale allotrope of carbon having several physiochemical properties such as high mechanical strength, high surface area, strong thermal and electrical conductivity makes it an important candidate in various modern applications such as drug delivery, supercapacitors, sensors etc. GO has been used in the photothermal treatment of cancers and Alzheimer’s disease etc. The main idea to choose GO in our work is that it is a surface active molecule, it has a large number of hydrophilic functional groups such as carboxylic acid, hydroxyl, epoxide on its surface and in basal plane. So it can easily interact with organic fluorophores through hydrogen bonding or any other kind of interaction and easily modulate the photophysics of the probe molecules. We have used different spectroscopic techniques for our work. The Ground-state absorption spectra and steady-state fluorescence emission spectra were measured by using UV-Vis spectrophotometer from Shimadzu (model-UV-2550) and spectrofluorometer from Horiba Jobin Yvon (model-Fluoromax 4P) respectively. All the fluorescence lifetime and anisotropy decays were collected by using time-correlated single photon counting (TCSPC) setup from Edinburgh instrument (model: LifeSpec-II, U.K.). Herein, we described the photophysics of a hydrophilic molecule 7-(n,n׀-diethylamino) coumarin-3-carboxylic acid (7-DCCA) in the reverse micelles containing GO. It was observed that photophysics of dye is modulated in the presence of GO compared to photophysics of dye in the absence of GO inside the reverse micelles. Here we have reported the solvent relaxation and rotational relaxation time in GO containing reverse micelle and compare our work with normal reverse micelle system by using 7-DCCA molecule. Normal reverse micelle means reverse micelle in the absence of GO. The absorption maxima of 7-DCCA were blue shifted and emission maxima were red shifted in GO containing reverse micelle compared to normal reverse micelle. The rotational relaxation time in GO containing reverse micelle is always faster compare to normal reverse micelle. Solvent relaxation time, at lower w₀ values, is always slower in GO containing reverse micelle compare to normal reverse micelle and at higher w₀ solvent relaxation time of GO containing reverse micelle becomes almost equal to normal reverse micelle. Here emission maximum of 7-DCCA exhibit bathochromic shift in GO containing reverse micelles compared to that in normal reverse micelles because in presence of GO the polarity of the system increases, as polarity increases the emission maxima was red shifted an average decay time of GO containing reverse micelle is less than that of the normal reverse micelle. In GO containing reverse micelle quantum yield, decay time, rotational relaxation time, solvent relaxation time at λₑₓ=375 nm is always higher than λₑₓ=405 nm, shows the excitation wavelength dependent photophysics of 7-DCCA in GO containing reverse micelles.

Keywords: photophysics, reverse micelle, rotational relaxation, solvent relaxation

Procedia PDF Downloads 155