Search results for: drug delivery systems

Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

Abstract:

Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two step wet chemical approach using NaBH4 as reducing agent for formation of Au inethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: core shell, drug delivery, gold nanoparticles, magnetic nanoparticles

Procedia PDF Downloads 375

Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

Abstract:

Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

Procedia PDF Downloads 515

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 141

Authors: Khushbu Priyadarshi, Chandramani Pathak

Abstract:

Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

Procedia PDF Downloads 149

Authors: Deepika Bhaskar, Neena Wadehra, Megha Gulati, Aruna Narula, R. Vishnu, Gunjan Katyal

Abstract:

With drug resistance becoming widespread in Plasmodium falciparum infections, development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of around 14000 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compare to reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results.

Keywords: plasmodium, malaria, drug targets, in silico studies

Procedia PDF Downloads 450

Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

Procedia PDF Downloads 584

Authors: Zahra Yadollahi, Marjan Motiei, Natalia Kazantseva, Petr Saha

Abstract:

Chitosan (CS)-whey protein isolate (WPI) core-shell nanoparticles were synthesized through self-assembly of whey protein isolated polyanions and chitosan polycations in the presence of tripolyphosphate (TPP) as a crosslinker. The formation of this type of nanostructures with narrow particle size distribution is crucial for developing delivery systems since the functional characteristics highly depend on their sizes. To achieve this goal, the nanostructure was optimized by varying the concentrations of WPI, CS, and TPP in the reaction mixture. The chemical characteristics, surface morphology, and particle size of the nanoparticles were evaluated.

Keywords: whey protein isolated, chitosan, nanoparticles, delivery system

Procedia PDF Downloads 94

Authors: Arindam Pramanik, Parimal Karmakar

Abstract:

We have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group (like curcumin) in metallorganic compound “Copper acetylacetonate” (CuAA). The cytotoxicity mechanism of CuAA complex was evaluated on various cancer cell lines in vitro. Among these, reactive oxygen species (ROS), glutathione level (GSH) in the cell was found to increase. Further mitochondrial membrane damage was observed. The fate of cell death was found to be induced by apoptosis. For application purpose, we have developed a novel biodegradable, non-toxic polymer-based nanoparticle which has hydrophobically modified core for loading of the CuAA. Folic acid is conjugated on the surface of the polymer (chitosan) nanoparticle for targeting to cancer cells for minimizing toxicity to normal cells in-vivo. Thus, this novel drug CuAA has an efficient anticancer activity which has been targeted specifically to cancer cells through polymer nanoparticle.

Keywords: anticancer, apoptosis, copper nanoparticle, targeted drug delivery

Procedia PDF Downloads 484

Authors: Naima Bouslah, Leila Bounabi, Farid Ouazib, Nabila Haddadine

Abstract:

Conventional release dosage forms are known to provide an immediate release of the drug. Controlling the rate of drug release from polymeric matrices is very important for a number of applications, particularly in the pharmaceutical area. Hydrogels are polymers in three-dimensional network arrangement, which can absorb and retain large amounts of water without dissolution. They have been frequently used to develop controlled released formulations for oral administration because they can extend the duration of drug release and thus reduce dose to be administrated improving patient compliance. Tramadol is an opioid pain medication used to treat moderate to moderately severe pain. When taken as an immediate-release oral formulation, the onset of pain relief usually occurs within about an hour. In the present work, we synthesized pH-responsive hydrogels of (hydroxyl ethyl methacrylate-co-acrylic acid), (HEMA-AA) for control drug delivery of tramadol in the gastro-intestinal tractus. The hydrogels with different acrylic acid content, were synthesized by free radical polymerization and characterized by FTIR spectroscopy, X ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). FTIR spectroscopy has shown specific hydrogen bonding interactions between the carbonyl groups of the hydrogels and hydroxyl groups of tramadol. Both the XRD and DSC studies revealed that the introduction of tramadol in the hydrogel network induced the amorphization of the drug. The swelling behaviour, absorptive kinetics and the release kinetics of tramadol in simulated gastric fluid (pH 1.2) and in simulated intestinal fluid (pH 7.4) were also investigated. The hydrogels exhibited pH-responsive behavior in the swelling study. The (HEMA-AA) hydrogel swelling was much higher in pH =7.4 medium. The tramadol release was significantly increased when pH of the medium was changed from simulated gastric fluid (pH 1.2) to simulated intestinal fluid (pH 7.4). Using suitable mathematical models, the apparent diffusional coefficients and the corresponding kinetic parameters have been calculated.

Keywords: biopolymres, drug delivery, hydrogels, tramadol

Procedia PDF Downloads 358

Authors: Faisal O. Al-Otaibi, Arthur T. Tucker, Richard M. Langford, Stuart Ratcliffe, Atholl Johnston, Terry D. Lee, Kenneth B. Kirby, Chandan A. Alam

Abstract:

The Transdermal Delivery System (TDS®) is a proprietary liquid formulation that can be applied to intact skin via a metered pump spray to facilitate drug delivery to the circulation. The aim of this study was to assess the ability of the TDS preparation to deliver diazepam systemically, and to characterize the pharmacokinetic profile of the drug in healthy adult subjects. We conducted a randomized, single-dose, two-period, crossover phase I (pharmacokinetic) comparative study in twelve healthy volunteers. All volunteers received both 10 mg TDS-diazepam topically to the upper chest and 10 mg of the rectal diazepam preparation (Diastat®, 10 mg diazepam gel), with a minimum washout of 14 days between dosing episodes. Both formulations were well tolerated in all volunteers. Following topical application of TDS-diazepam, the mean AUC0-72h was 1241 ng/mL.h and the Cmax 34 ng/mL. The values for rectal Diastat were 4109 ng/mL.h and 300 ng/mL respectively. This proof of concept study demonstrates that the TDS preparation successfully delivered diazepam systemically to adults. As expected, the concentration of diazepam following the TDS application was lower and not bioequivalent to rectal gel. Future development of this unique system is required.

Keywords: transdermal delivery system, diazepam, seizure, bioequivalence, pharmacokinetic

Procedia PDF Downloads 426

Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

Abstract:

The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

Procedia PDF Downloads 82

Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

Abstract:

The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF, and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

Procedia PDF Downloads 161

Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

Abstract:

Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

Procedia PDF Downloads 454

Authors: Ying Bo Xie, Hisa Yuki Kurokawa

Abstract:

Due to the fast development, China's express delivery industry has involved in a dilemma that the service quality are keeping decreasing while the construction rate of delivery network cannot meet the customers’ demand. In order to get out of this dilemma and enjoy a succession development rate, it is necessary to understand the current situation of China's express delivery industry. Firstly, the evolution of China's express delivery industry was systematical presented. Secondly, according to the number of companies and the amount of parcels they has dealt each year, the merits and faults of tow kind of operating pattern was analyzed. Finally, based on the characteristics of these express companies, the problems of China's express delivery industry was divided into several types and the countermeasures were given out respectively.

Keywords: China, express delivery industry, status, problem

Procedia PDF Downloads 364

Authors: Hind Bouami, Patrick Millot

Abstract:

Medication dispensing system is a life-critical system whose failure may result in preventable adverse events leading to longer patient stays in hospitals or patient death. Automation has led to great improvements in life-critical systems as it increased safety, efficiency, and comfort. However, critical risks related to medical organization complexity and automated solutions integration can threaten drug dispensing security and performance. Knowledge about the system’s complexity aspects and human machine parameters to control for automated equipment’s security and performance will help operators to secure their automation process and to optimize their system’s reliability. In this context, this study aims to document the operator’s situation awareness about automation risks and parameters involved in automation security and performance. Our risk management approach has been deployed in the North Luxembourg hospital center’s pharmacy, which is equipped with automated drug dispensing systems since 2009. With more than 4 million euros of gains generated, North Luxembourg hospital center’s success story was enabled by the management commitment, pharmacy’s involvement in the implementation and improvement of the automation project, and the close collaboration between the pharmacy and Sinteco’s firm to implement the necessary innovation and organizational actions for automated solutions integration security and performance. An analysis of the actions implemented by the hospital and the parameters involved in automated equipment’s integration security and performance has been made. The parameters to control for automated equipment’s integration security and performance are human aspects (6.25%), technical aspects (50%), and human-machine interaction (43.75%). The implementation of an anthropocentric analysis system before automation would have prevented and optimized the control of risks related to automation.

Keywords: Automated drug delivery systems, Hospitals, Human-centered automated system, Risk management

Procedia PDF Downloads 137

Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

Abstract:

Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

Procedia PDF Downloads 149

Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

Abstract:

Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

Procedia PDF Downloads 231

Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

Abstract:

—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.

Keywords: antibacterial, bioglass, drug delivery system, sol- gel

Procedia PDF Downloads 61

Authors: Pravina Gurjar, Bothiraja Pour, Vijay Kumbhar, Ganesh Dama

Abstract:

Andrographolide (AG), a bioactive phytoconstituent, has a wider range of pharmacological action. However, due to the intestinal degradation, shows low oral bioavailability. The aim of the present work was to develop Floating In-situ gelling Gastro retentive System (FISGS) for AG in order to enhance its site specific absorption and minimize pH dependent hydrolysis in alkaline environment. Further to increase its therapeutic efficacy for peptic ulcer disease caused by H. pyroli. Gellan based floating in situ gelling system of AG were prepared by using sodium citrate and calcium carbonate. The 32 factorial designs was used to study the effect of gellan and calcium carbonate concentration (independent variables) on dependent variable such as viscosity, floating lag time and drug release. Developed system was evaluated for drug content, floating lag time, viscosity, and drug release studies. Drug content, viscosity, and floating lag time was found to be 81-99%, 67-117 Cps, and 3-5 sec, respectively. The obtained system showed good in vitro floating ability for more than 12 h using 0.1 N HCl as dissolution medium with initial burst release followed by the controlled zero order drug release up to 24 hrs. In vivo testing of FISGS of AG to rats demonstrated significant antiulcer activity that were evaluated by various parameters like pH, volume, total acidity, millimole equivalent of H+ ions/30 min, and protein content of gastric content. The densities of all the formulation batches were found to be near about 0.9 and floating duration above 12 hr. It was observed that with the increase in conc. of gellan there was increase in the viscosity of formulation but all formulations were in optimum range. The drug content of optimized batch was found to be 99.23. In histopathology study of stomach, the villi at the mucosal surface, the intercellular junction, the intestinal lumen were intact; no destruction of the epithelium, and submucosal gland in formulation treated and control group animals as compared to pure drug AG and standard ranitidine. Gellan-based in situ gastro retentive floating system could be advantageous in terms of increased bioavailability of AG to maintain an effective drug conc. in gastric fluid as well as in serum for longer period of time.

Keywords: andrographolide, floating drug delivery, in situ gelling system, gastroretentive system

Procedia PDF Downloads 363

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

Abstract:

Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

Procedia PDF Downloads 331

Authors: Colette Malyack, Pius Egbelu

Abstract:

Business-to-Customer (B2C) delivery options have improved to meet increased demand in recent years. The change in end users has forced logistics networks to focus on customer service and sentiment that would have previously been the priority of the company or organization of origin. This has led to increased pressure on logistics companies to extend traditional B2B networks into a B2C solution while accommodating additional costs, roadblocks, and customer sentiment; the result has been the creation of the omnichannel delivery network encompassing a number of traditional and modern methods of package delivery. In this paper the many solutions within the omnichannel delivery network are defined and discussed. It can be seen through this analysis that the omnichannel delivery network can be applied to reduce the complexity of package delivery and provide customers with more options. Applied correctly the result is a reduction in cost to the logistics company over time, even with an initial increase in cost to obtain the technology.

Keywords: network planning, last mile delivery, omnichannel delivery network, omnichannel logistics

Procedia PDF Downloads 150

Authors: Haile F. Darge, Hsieh C. Tsai

Abstract:

The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

Procedia PDF Downloads 134

Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

Abstract:

In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

Procedia PDF Downloads 248

Authors: Kyou Hee Shim, Hwa Sung Shin

Abstract:

When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

Procedia PDF Downloads 227

Authors: Pramod Jagtap, Kisan Jadhav, Neha Dand

Abstract:

Risperidone (RISP) is an antipsychotic agent and has low water solubility and nontargeted delivery results in numerous side effects. Hence, an attempt was made to develop SLNs hydrogel for intranasal delivery of RISP to achieve maximum bioavailability and reduction of side effects. RISP loaded SLNs composed of 1.65% (w/v) lipid mass were produced by high shear homogenization (HSH) coupled ultrasound (US) method using glyceryl monostearate (GMS) or Imwitor 900K (solid lipid). The particles were loaded with 0.2% (w/v) of the RISP & surface-tailored with a 2.02% (w/v) non-ionic surfactant Tween® 80. Optimization was done using 32 factorial design using Design Expert® software. The prepared SLNs dispersion incorporated into Polycarbophil AA1 hydrogel (0.5% w/v). The final gel formulation was evaluated for entrapment efficiency, particle size, rheological properties, X ray diffraction, in vitro diffusion, ex vivo permeation using sheep nasal mucosa and histopathological studies for nasocilliary toxicity. The entrapment efficiency of optimized SLNs was found to be 76 ± 2 %, polydispersity index <0.3., particle size 278 ± 5 nm. This optimized batch was incorporated into hydrogel. The pH was found to be 6.4 ± 0.14. The rheological behaviour of hydrogel formulation revealed no thixotropic behaviour. In histopathology study, there was no nasocilliary toxicity observed in nasal mucosa after ex vivo permeation. X-ray diffraction data shows drug was in amorphous form. Ex vivo permeation study shows controlled release profile of drug.

Keywords: ex vivo, particle size, risperidone, solid lipid nanoparticles

Procedia PDF Downloads 419

Authors: Pimporn Thongmuang

Abstract:

The import value of antimicrobial drugs reached approximately fifteen million Baht in 2010, considered as the highest import value of all modern drugs, and this value is rising every year. Antimicrobials are considered the hazardous drugs by the Ministry of Public Health. This research was conducted in order to investigate the past knowledge of drug use and Antimicrobial drug use behavior. A total of 757 students were selected as the samples out of a population of 1,800 students. This selected students had the experience of Antimicrobial drugs use a year ago. A questionnaire was utilized in this research. The findings put on the view that knowledge gained by the students about proper use of antimicrobial drugs was not brought into practice. This suggests that the education procedure regarding drug use needs adjustment. And therefore the findings of this research are expected to be utilized as guidelines for educating people about the proper use of antimicrobial drugs. At a broader perspective, correct drug use behavior of the public may potentially reduce drug cost of the Ministry of Public Health of Thailand.

Keywords: drug use knowledge, antimicrobial drugs, drug use behavior, drug

Procedia PDF Downloads 280

Authors: S. L. J. Tan, N. Billa, C. J. Roberts

Abstract:

Oral delivery of amphotericin B (AmpB) potentially eliminates constraints and side effects associated with intravenous administration, but remains challenging due to the physicochemical properties of the drug such that it results in meagre bioavailability (0.3%). In an advanced formulation, 1) nanostructured lipid carriers (NLC) were formulated as they can accommodate higher levels of cargoes and restrict drug expulsion and 2) a mucoadhesion feature was incorporated so as to impart sluggish transit of the NLC along the gastrointestinal tract and hence, maximize uptake and improve bioavailability of AmpB. The AmpB-loaded NLC formulation was successfully formulated via high shear homogenisation and ultrasonication. A chitosan coating was adsorbed onto the formed NLC. Physical properties of the formulations; particle size, zeta potential, encapsulation efficiency (%EE), aggregation states and mucoadhesion as well as the effect of the variable pH on the integrity of the formulations were examined. The particle size of the freshly prepared AmpB-loaded NLC was 163.1 ± 0.7 nm, with a negative surface charge and remained essentially stable over 120 days. Adsorption of chitosan caused a significant increase in particle size to 348.0 ± 12 nm with the zeta potential change towards positivity. Interestingly, the chitosan-coated AmpB-loaded NLC (ChiAmpB NLC) showed significant decrease in particle size upon storage, suggesting 'anti-Ostwald' ripening effect. AmpB-loaded NLC formulation showed %EE of 94.3 ± 0.02 % and incorporation of chitosan increased the %EE significantly, to 99.3 ± 0.15 %. This suggests that the addition of chitosan renders stability to the NLC formulation, interacting with the anionic segment of the NLC and preventing the drug leakage. AmpB in both NLC and ChiAmpB NLC showed polyaggregation which is the non-toxic conformation. The mucoadhesiveness of the ChiAmpB NLC formulation was observed in both acidic pH (pH 5.8) and near-neutral pH (pH 6.8) conditions as opposed to AmpB-loaded NLC formulation. Hence, the incorporation of chitosan into the NLC formulation did not only impart mucoadhesive property but also protected against the expulsion of AmpB which makes it well-primed as a potential oral delivery system for AmpB.

Keywords: Amphotericin B, mucoadhesion, nanostructured lipid carriers, oral delivery

Procedia PDF Downloads 162

Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

Abstract:

Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

Procedia PDF Downloads 307

Authors: Sharif Abdelghany

Abstract:

Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

Procedia PDF Downloads 367

Authors: Yaowaporn Sangsen, Kittisak Likhitwitayawuid, Boonchoo Sritularak, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

Abstract:

Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol® 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. In vitro drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system to develop for the oral OXY delivery.

Keywords: solid lipid nanoparticles, physicochemical properties, in vitro drug release, oxyresveratrol

Procedia PDF Downloads 397