Search results for: targeted drug delivery

Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

Abstract:

Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

Procedia PDF Downloads 93

Authors: Alfred L. Guiffrida

Abstract:

A review of the literature on supply chain delivery models which use delivery windows to measure delivery performance is presented. The review herein serves to meet the following objectives: (i) provide a synthesis of previously published literature on supply chain delivery performance models, (ii) provide in one paper a consolidation of research that can serve as a single source to keep researchers up to date with the research developments in supply chain delivery models, and (iii) identify gaps in the modeling of supply chain delivery performance which could stimulate new research agendas.

Keywords: delivery performance, delivery window, supply chain delivery models, supply chain performance

Procedia PDF Downloads 387

Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

Abstract:

A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

Procedia PDF Downloads 510

Authors: A. Banerjee, C. Grazon, B. Nadal, T. Pons, Y. Krishnan, B. Dubertret

Abstract:

Quantum Dots (QDs) have emerged as novel fluorescent probes for biomedical applications. The photophysical properties of QDs such as broad absorption, narrow emission spectrum, reduced blinking, and enhanced photostability make them advantageous over organic fluorophores. However, for some biological applications, QDs need to be first targeted to specific intracellular locations. It parallel, base pairing properties and biocompatibility of DNA has been extensively used for biosensing, targetting and intracellular delivery of numerous bioactive agents. The combination of the photophysical properties of QDs and targettability of DNA has yielded fluorescent, stable and targetable nanosensors. QD-DNA conjugates have used in drug delivery, siRNA, intracellular pH sensing and several other applications; and continue to be an active area of research. In this project, a novel method to synthesise QD-DNA conjugates and their applications in bioimaging are investigated. QDs are first solubilized in water using a thiol based amphiphilic co-polymer and, then conjugated to amine functionalized DNA using a heterobifunctional linker. The conjugates are purified by size exclusion chromatography and characterized by UV-Vis absorption and fluorescence spectroscopy, electrophoresis and microscopy. Parameters that influence the conjugation yield such as reducing agents, the excess of salt and pH have been investigated in detail. In optimized reaction conditions, up to 12 single-stranded DNA (15 mer length) can be conjugated per QD. After conjugation, the QDs retain their colloidal stability and high quantum yield; and the DNA is available for hybridization. The reaction has also been successfully tested on QDs emitting different colors and on Gold nanoparticles and therefore highly generalizable. After extensive characterization and robust synthesis of QD-DNA conjugates in vitro, the physical properties of these conjugates in cellular milieu are being invistigated. Modification of QD surface with DNA appears to remarkably alter the fate of QD inside cells and can have potential implications in therapeutic applications.

Keywords: bioimaging, cellular targeting, drug delivery, photostability

Procedia PDF Downloads 396

Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

Abstract:

Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

Procedia PDF Downloads 333

Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

Abstract:

Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

Procedia PDF Downloads 216

Authors: Simone Galati, Adriano Troia

Abstract:

Ultrasound (US) is widely used in medical field for a variety diagnostic techniques but, in recent years, it has also been creating great interest for therapeutic aims. Regarding drug delivery, the use of US as an activation source provides better spatial delivery confinement and limits the undesired side effects. However, at present there is no complete characterization at a fundamental level of the different signals produced by sono-activated nanocarriers. Therefore, the aim of this study is to obtain a metrological characterization of the cavitation phenomena induced by US through three parallel investigation approaches. US was focused into a channel of a customized phantom in which a solution with oxygen-loaded nanodroplets (OLNDs) was led to flow and the cavitation activity was monitored. Both quantitative and qualitative real-time analysis were performed giving information about the dynamics of bubble formation, oscillation and final implosion with respect to the working acoustic pressure and the type of nanodroplets, compared with pure water. From this analysis a possible interpretation of the observed results is proposed.

Keywords: cavitation, drug delivery, nanodroplets, ultra-sound

Procedia PDF Downloads 78

Authors: Meltem Haktaniyan, Eda Cagli, Irem Erel Goktepe

Abstract:

Polymers that change their properties in response to different stimuli (e.g. light, temperature, pH, ionic strength or magnetic field) are called ‘smart’ or ‘stimuli-responsive polymers’. These polymers have been widely used in biomedical applications such as sensors, gene delivery, drug delivery or tissue engineering. Temperature-responsive polymers have been studied extensively for controlled drug delivery applications. As regard of pseudo-peptides, poly (2-alky-2-oxazoline)s are considered as good candidates for delivery systems due to their stealth behavior and nontoxicity. In order to build responsive multilayer films for controlled drug release applications from surface, Layer by layer technique (LBL) is a powerful technique with an advantage of nanometer scale control over spatial architecture and morphology. Multilayers can be constructed on surface where non-covalent interactions including electrostatic interactions, hydrogen bonding, and charge-transfer or hydrophobic-hydrophobic interactions. In the present study, hydrogen bounded multilayer films of poly (2-alky-2-oxazoline) s with tannic acid were prepared in order to use as a platform to release Doxorubicin (DOX) from surface with pH and thermal triggers. For this purpose, poly (2-isopropyl-2-oxazoline) (PIPOX) and poly (2-ethyl-2-oxazoline) (PETOX) were synthesized via cationic ring opening polymerization (CROP) with hydroxyl end groups. Two polymeric multilayer systems ((PETOX)/(DOX)-(TA) complexes and (PIPOX)/(DOX)-(TA) complexes) were designed to investigate of controlled release of Doxorubicin (DOX) from surface with pH and thermal triggers. The drug release profiles from the multilayer thin films with alterations of pH and temperature will been examined with UV-Vis Spectroscopy and Fluorescence Spectroscopy.

Keywords: temperature responsive polymers, h-bonded multilayer films, drug release, polyoxazoline

Procedia PDF Downloads 284

Authors: Yann Jean Tan, Hui Meng Er, Choy Sin Lee, Shew Fung Wong, Wen Huei Lim

Abstract:

Griseofulvin is a long standing fungistatic agent against dermatophytosis. Nevertheless, it has several drawbacks such as poor and highly variable bio availability, long duration of treatment, systemic side effects and drug interactions. Targeted treatment for the superficial skin infection, dermatophytosis via topical route could be beneficial. Nevertheless, griseofulvin is only available in the form of oral preparation. Hence, it generates interest in developing a topical formulation for griseofulvin, by using lipid nano particle as the vehicle. Lipid nanoparticle is a submicron colloidal carrier with a core that is solid in nature (lipid). It has combined advantages of various traditional carriers and is a promising vehicle for topical delivery. The griseofulvin loaded lipid nano particles produced using high pressure homogenization method were characterized and investigated for its skin targeting effect in vitro. It has a mean particle size of 179.8±4.9 nm with polydispersity index of 0.306±0.011. Besides, it showed higher skin permeation and better skin targeting effect compared to the griseofulvin suspension.

Keywords: lipid nanoparticles, griseofulvin, topical, dermatophytosis

Procedia PDF Downloads 426

Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

Abstract:

Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

Procedia PDF Downloads 458

Authors: Meenu Mehta, Munish Garg

Abstract:

The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.

Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS

Procedia PDF Downloads 276

Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

Abstract:

Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

Procedia PDF Downloads 125

Authors: Chieh-Nan Chen, Ji-Yu Lin, I-Ming Chu

Abstract:

Polypeptide thermosensitive hydrogel is an excellent candidate as a smart device to deliver drugs and cells due to its remarkable biocompatibility, low gelation concentration, and respond to temperature stimuli, it can be easily injected as a polymer solution into the patient’s body where it undergoes gelation due to an elevation in temperature. Poly (ethylene glycol) monomethyl ether-poly (ethyl-l-glutamate) (mPEG-PELG) contains a hydrophobic side chain –C2H5 which is useful in encapsulating and stabilizing hydrophobic drugs. In this study, we plan to focus on the hydrophobic anti-carcinogenic and anti-inflammatory drug curcumin, which due its insolubility in water, requires a proper carrier for delivery into the body. Our main concept is to use mPEG-PELG to stabilize curcumin, inject the curcumin-loaded hydrogel into the tumor site, and allow the enzymatically-sensitive hydrogel to be degraded by bodily fluids and release the drug. The polymers of interest have been successfully synthesized and characterized by 1H-NMR, FT-IR, SEM, and CMC. Curcumin loading content and drug release were assayed using HPLC. Preliminary results show that these materials have potential as a delivery vehicle for poorly soluble drugs.

Keywords: curcumin, drug release, hydrogel, polypeptide material

Procedia PDF Downloads 271

Authors: Calvin A. Omolo, Rahul S. Kalhapure, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender

Abstract:

Treatment of infections is compromised by limitations of conventional dosage forms and drug resistance. Nanocarrier system is a strategy to overcome these challenges and improve therapy. Thus, the development of novel materials for drug delivery via nanocarriers is essential. The aim of the study was to synthesize a multi-arm polymer (6-mPEPEA) for enhanced activity of vancomycin (VM) against susceptible and resistant Staphylococcus aureus (MRSA). The synthesis steps of the star polymer followed reported procedures. The synthesized 6-mPEPEA was characterized by FTIR, ¹H and ¹³CNMR and MTT assays. VM loaded micelles were prepared from 6-mPEPEA and characterized for size, polydispersity index (PI) and surface charge (ZP) (Dynamic Light Scattering), morphology by TEM, drug loading (UV Spectrophotometry), drug release (dialysis bag), in vitro and in vivo efficacy against sensitive and resistant S. aureus. 6-mPEPEA was synthesized, and its structure was confirmed. MTT assays confirmed its nontoxic nature with a high cell viability (77%-85%). Unimolecular spherical micelles were prepared. Size, PI, and ZP was 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV, respectively and drug loading was 62.24 ± 3.8%. There was a 91% drug release from VCM-6-mPEPEA after 72 hours. In vitro antibacterial test revealed that VM-6-mPEPEA had 8 and 16-fold greater activity against S. aureus and MRSA when compared to bare VM. Further investigations using flow cytometry showed that VM-6-mPEPEA had 99.5% killing rate of MRSA at the MIC concentration. In vivo antibacterial activity revealed that treatment with VM-6-mPEPEA had a 190 and a 15-fold reduction in the MRSA load in untreated and VM treated respectively. These findings confirmed the potential of 6-mPEPEA as a promising bio-degradable nanocarrier for antibiotic delivery to improve treatment of bacterial infections.

Keywords: biosafe, MRSA, nanocarrier, resistance, unimolecular-micelles

Procedia PDF Downloads 153

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 344

Authors: Vishal Kumar Gupta

Abstract:

Purpose: This study has been undertaken to develop novel pH sensitive interpenetrating network hydrogel beads. Methods: The pH sensitive PAAM-g-Guar gum copolymer was synthesized by free radical polymerization followed by alkaline hydrolysis. Beads of guar gum-grafted-polyacrylamide and sodium Carboxy methyl cellulose (Na CMC) loaded with Pantoprazole sodium were prepared and evaluated for pH sensitivity, swelling properties, drug entrapment efficiency and in vitro drug release characteristics. Seven formulations were prepared for the drug with varying polymer and cross linker concentrations. Results: The grafting and alkaline hydrolysis reactions were confirmed by FT-IR spectroscopy. Differential scanning calorimetry was carried out to know the compatibility of encapsulated drug with the polymers. Scanning electron microscopic study revealed that the IPN beads were spherical. The entrapment efficiency was found to be in the range of 85-92%. Particle size analysis was carried out by optical microscopy. As the pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all beads. Increase in the copolymer concentration showed sustained the drug release up to 12 hrs. Drug release from the beads followed super case II transport mechanism. Conclusion: It was concluded that guar gum-acrylamide beads, cross-linked with aluminum chloride offer an opportunity for controlled drug release of pantoprazole sodium.

Keywords: IPN, hydrogels, DSC, SEM

Procedia PDF Downloads 249

Authors: Raquel Galante, Marina Braga, Daniela Ghisleni, Terezinha J. A. Pinto, Rogério Colaço, Ana Paula Serro

Abstract:

The sensitive nature of soft biomaterials, such as hydrogels, renders their sterilization a particularly challenging task for the biomedical industry. Widely used contact lenses are now studied as promising platforms for topical corneal drug delivery. However, to the best of the authors knowledge, the influence of sterilization methods on these systems has yet to be evaluated. The main goal of this study was to understand how different pairs drug-hydrogel would interact under an ozone-based sterilization method in comparison with two conventional processes (steam heat and gamma irradiation). For that, Si-Hy containing hydroxylethyl methacrylate (HEMA) and [tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) was produced and soaked in different drug solutions, commonly used for the treatment of ocular diseases (levofloxacin, chlorhexidine, diclofenac and timolol maleate). The drug release profiles and main material properties were evaluated before and after the sterilization. Namely, swelling capacity was determined by water uptake studies, transparency was accessed by UV-Vis spectroscopy, surface topography/morphology by scanning electron microscopy (SEM) and mechanical properties by performing tensile tests. The drug released was quantified by high performance liquid chromatography (HPLC). The effectiveness of the sterilization procedures was assured by performing sterility tests. Ozone gas method led to a significant reduction of drug released and to the formation of degradation products specially for diclofenac and levofloxacin. Gamma irradiation led to darkening of the loaded Si-Hys and to the complete degradation of levofloxacin. Steam heat led to smoother surfaces and to a decrease of the amount of drug released, however, with no formation of degradation products. This difference in the total drug released could be the related to drug/polymer interactions promoted by the sterilization conditions in presence of the drug. Our findings offer important insights that, in turn, could be a useful contribution to the safe development of actual products.

Keywords: drug delivery, silicone hydrogels, sterilization, gamma irradiation, steam heat, ozone gas

Procedia PDF Downloads 285

Authors: Caroline Mendes, Mary McNamara, Orla Howe

Abstract:

Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

Procedia PDF Downloads 281

Authors: Surendra Agrawal, Pravina Gurjar, Supriya Bhide, Ram Gaud

Abstract:

Levamisole hydrochloride is a prominent anticancer drug in the treatment of colon cancer but resulted in toxic effects due poor bioavailability and poor cellular uptake by tumor cells. Levamisole is an unstable drug. Incorporation of this molecule in solid lipids may minimize their exposure to the aqueous environment and partly immobilize the drug molecules within the lipid matrix-both of which may protect the encapsulated drugs against degradation. The objectives of the study were to enhance bioavailability by sustaining drug release and to reduce the toxicities associated with the therapy. Solubility of the drug was determined in different lipids to select the components of Solid Lipid Nanoparticles (SLN). Pseudoternary phase diagrams were created using aqueous titration method. Formulations were subjected to particle size and stability evaluation to select the final test formulations which were characterized for average particle size, zeta potential, and in-vitro drug release and percentage transmittance to optimize the final formulation. SLN of Levamisole hydrochloride was prepared by Nanoprecipitation method. Glyceryl behenate (Compritol 888 ATO) was used as core comprising of Tween 80 as surfactant and Lecithin as co-surfactant in (1:1) ratio. Entrapment efficiency (EE) was found to be 45.89%. Particle size was found in the range of 100-600 nm. Zeta potential of the formulation was -17.0 mV revealing the stability of the product. In-vitro release study showed that 66 % drug released in 24 hours in pH 7.2 which represent that formulation can give controlled action at the intestinal environment. In pH 5.0 it showed 64% release indicating that it can even release drug in acidic environment of tumor cells. In conclusion, results revealed SLN to be a promising approach to sustain the drug release so as to increase bioavailability and cellular uptake of the drug with reduction in toxic effects as dose has been reduced with controlled delivery.

Keywords: SLN, nanoparticulate delivery of levamisole, pharmacy, pharmaceutical sciences

Procedia PDF Downloads 403

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

Abstract:

In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

Procedia PDF Downloads 164

Authors: Abbas Jafarizad, Duygu Ekinci

Abstract:

In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.

Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells

Procedia PDF Downloads 244

Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

Abstract:

Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

Procedia PDF Downloads 288

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

Abstract:

Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

Procedia PDF Downloads 369

Authors: S. Bouameur, S. Chirani

Abstract:

The aim of this study was to evaluate the potential use of EthylCellulose in the preparation of microspheres as a Drug Delivery System for sustained release of phenobarbital. The microspheres were prepared by solvent evaporation technique using ethylcellulose as polymer matrix with a ratio 1:2, dichloromethane as solvent and Polyvinyl alcohol 1% as processing medium to solidify the microspheres. Size, shape, drug loading capacity and entrapement efficiency were studied.

Keywords: phenobarbital, microspheres, ethylcellulose, polyvinylacohol

Procedia PDF Downloads 339

Authors: Mohammad Yousef

Abstract:

The issue of targeted killing has become a part of modern international law topics, as its spread has been accompanied by the technological development of weapons and military equipment, especially armed drones. Until now, there is no specific definition or legal framework for targeted killing in international law, and the issue of its compatibility with international law is still subject to debate and controversy. The case of the targeted killing of General Qassem Soleimani sparked waves of reactions and discussions between legal scholars and US officials in an argument about the legality of killing him in the light of international law rules and US domestic law. This paper firstly discusses the legality of targeted killing in international law and US domestic law; after that, it studies the legal bases and the legal system that governs these operations, while in the second section, it sheds light on the case of Soleimani’s targeted killing in light of international law and US domestic law, by examining the different views of jurists in this regard.

Keywords: targeted killing, international law, US domestic law, Qassem Soleimani

Procedia PDF Downloads 103

Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

Abstract:

Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

Procedia PDF Downloads 102

Authors: Yasmin Begum Mohammed

Abstract:

Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

Procedia PDF Downloads 271

Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

Procedia PDF Downloads 462

Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

Abstract:

Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

Procedia PDF Downloads 455

Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

Abstract:

Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

Procedia PDF Downloads 234