5-Fluorouracil-Impregnated PLGA Coated Gold Nanoparticles for Augmented Delivery to Lung Cancer: in vitro Investigations

Background and Objective: The study aimed to investigate the augmented cytotoxic effects of polymer-coated (poly-lactic-co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management of lung cancer. Materials and Methods: In this study, several formulations were prepared using a double emulsion (water-oil-water) method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment. Results: Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. The optimized polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09 ± 10.75%) compared to others. The percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles (FGNPs), (PFGNPs) and 5-FU solution were 47.87± 1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively, over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of PFGNPs on the A549 cells was 82.89 % compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for PFNPs. Conclusion: PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung cancer with reduced toxicity and improved efficacy.

Development and Evaluation of Nanoparticles Based Topical Gel Containing Antifungal Drug Fluconazole

The objective of this work was to prepare Fluconazole nanoparticles, and then incorporated into the freshly prepared gel for transdermal delivery, reducing the oral side effects of the drug and forenhancing stability. Fluconazole is commonly used antifungal agents for the treatment of local and systemic fungal infections. In this study Fluconazole nanoparticles was prepared by using Eudragit RL 100 by nanoprecipitation method with different drugs to polymer (1:1, 1:2 and 1:3) and stabilizer (Poloxamer 188) ratios (0.5%, 0.75% and 1%) and evaluated for various parameters. Drug-excipients compatibility was performed by FTIR study. The particle size, polydispersity index, Zeta potential, % Entrapment efficiency and % drug content of all the formulations were found in the range of 16.8 to 48.9nm, 0.229 to 0.558, -11.6 to -26.6 mv, 28.41% to 95.78% and 59% to 97.38%. From SEM studies it was revealed that Fluconazole nanoparticles particles are spherical in shape and without any agglomeration. From the in-vitro drug release study, it was revealed that sustained release of same formulation last up to 12 hours. From the stability study, it was revealed that the F5 formulation was stable at 40°C ± 2°C /75% ± 5%RH and 4°C. The optimised formulation F5 was selected to prepare Fluconazole loaded nanoparticles based topical gels using different concentration of Carbopol 934 and 940 and characterized for pH, spreadability, drug content, viscosity and in-vitro drug diffusion. Among the five formulations, G5 was selected as the best formulation. The pH of all formulations was found near to the skin pH value. The in-vitrodiffusion study of Fluconazole gel (G5) showed 94.75%. The optimized formulation G5 was checked for mechanism and kinetics of drug release. It is found it following Zero order release and non-Fickian mechanism. The selected Gel formulation G5 was found to be stable at 40°C ± 2°C /75% ± 5%RH and 4°C, it is clear that the formulation did not undergo any chemical changes found more stable at room temperature

Effect of Organogelator Concentration on Gelation Kinetics and Drug Release Behaviour of Paracetamol-Loaded Soybean Oleogels

Organogelators induce 3-D networked structures in apolar solvent molecules via cross-linking of non-covalent self-assembled aggregates below the gelation temperature. The objective of the present investigation was to evaluate the effects of different Span 40 concentrations on gelation kinetics and drug release behaviour of topical soybean oleogels. An inversely proportional relationship was observed between gelation time, melt flow index and concentration of Span 40 in soybean oleogels. Gompertz model was employed on gelation kinetics data to determine organogelator and oil parameters which are assumed to be associated with thermal stability and gel flexibility respectively. Formulation OGS2 (18% W/V Span 40) formed less viscous, thermally stable and presumably more flexible oleogel compared to other formulations. Nearly ideal zero-order release of paracetamol was achieved from OGS*2 following Fickian diffusion. However, slow drug release profiles, higher t50 values were observed with oleogels having 20-24% w/v Span 40 which followed Korsmeyer-Peppas kinetics with non-Fickian diffusion.

Formulation and evaluation of proniosome loaded sertaconazole nitrate for topical application

Proniosomal technology is a novel solution for poorly soluble drugs. Proniosomes are water-soluble carrier particles which are coated with non-ionic surfactants. Proniosomal gels were prepared by coacervation phase separation method using non-ionic surfactants, lipid carriers and cholesterol as a membrane stabilizer. FTIR compatibility studies revealed that the drug and excipients were compatible. All formulations were evaluated for pH, drug content, extrudability, spreadability, viscosity, in-vitro, ex-vivo, skin irritation and stability studies. Among formulations prepared, F80H1 has shown higher % EE (83.02) and least diffusion through dialysis membrane i.e., 17.68%. With ex-vivo studies, F80H1 formulation has shown highest skin deposition and lower flux of sertaconazole nitrate through the rat skin. F80H1 was selected as final optimized formulation. F80H1 exhibited good stability and SEM studies revealed that the vesicles were spherical in shape. The optimized formulation was found to follow zero order release kinetics and korsmeyer-peppas release mechanism. F80H1 found to be non-irritant and stable from skin irritation and stability studies.

Development and Evaluation of Trans Buccal Patches based on Natural and Synthetic Polymers Loaded with Rivastigmine using Solvent Casting Technique

Mucoadhesive buccal films of rivastigmine were prepared by the solvent casting technique using HPMC K15M, sodium alginate, glycerine, and Eudragit RL100. Arranged films assessed for weight variation, thickness, % drug substance, % moisture loss, % moisture take-up, folding endurance, in-vitro medicament release, and Fourier transform Infrared spectroscopy (FTIR). The films showed a controlled release (CR) over 8 h. The preparation observed to be a worthy candidate for the development of buccal patches for therapeutic purposes. Drug-polymer compatibility considers FTIR demonstrated no contradiction between the medicament and the polymers. The optimized formulation found F7 indicated drug release 85% at the end of 8 h. Thinking about the correlation coefficient (R2) values got from the kinetic equations, the drug release from the formulations F1-F8 has discovered zero-order release mechanism. It can be concluded that oral buccal patches of rivastigmine, for treatment of Alzheimer’s and Parkinson’s disease, can be formulated. The study suggests that rivastigmine can be conveniently administered orally in the form of buccal patches, with the lesser occurrence of its side effects and improved bioavailability.

Double-Walled Poly-(D,L-lactide-co-glycolide) (PLGA) and Poly(L-lactide) (PLLA) Nanoparticles for the Sustained Release of Doxorubicin

Double-walled nanoparticles (DWNPs), containing doxorubicin as a model drug, were produced using poly-(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by the solvent evaporation technique. Double-walled microparticles containing doxorubicin were also produced to make possible the examination of the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles present a double-walled structure with doxorubicin solubilized in the PLGA-rich phase. The DWNPs produced present very low initial burst values and a sustained DOX release for at least 90 days with release rates decreasing with the increase in the PLLA amount. Zero-order release kinetics were obtained after day 15. The results support that the PLLA layer acts as a rate control barrier and that the diffusion of doxorubicin from the drug-loaded inner PLGA core can be retarded by an increase in the thickness of the unloaded outer layer. The unloaded double-walled nanoparticles produced were used in in vitro tests with CHO cells and demonstrate that they are nontoxic, while the double-walled nanoparticles loaded with doxorubicin caused a great cellular viability and decreased when tested in vitro.

Bacteriophage Delivery Systems Based on Composite PolyHIPE/Nanocellulose Hydrogel Particles

The role of bacteriophage therapy in medicine has recently regained an important place. Oral phage delivery for gastrointestinal treatment, transport through the stomach, and fast release in the duodenum is one of such applications. In this work, an efficient polyHIPE/hydrogel system for targeted delivery of bacteriophages with rapid release at the target site is presented. T7 bacteriophages were encapsulated in low crosslinked anionic nanocellulose-based hydrogels, which successfully protected phages at pH < 3.9 (stomach) and completely lost the hydrogel network at a pH above 3.9 (duodenum), allowing their release. Hydrogels with entrapped phages were crosslinked within highly porous spherical polyHIPE particles with an average diameter of 24 μm. PolyHIPE scaffold protects the hydrogels from mechanical stimuli during transport, preventing the collapse of the hydrogel structure and the unwanted phage release. On the other hand, small particle size, due to the large surface-to-volume ratio, enables rapid release at the target site. As a consequence, a fast zero-order release was achieved, providing improved patient compliance and reduced frequency of drug administration. The proposed system therefore exhibits significant potential for a targeted drug delivery in medicine and pharmacy.

Design and Evaluation of Acyclovir Niosomes

The current study aims to formulate and evaluate acyclovir loaded niosomes for sustained release of acyclovir. Stable Acyclovir loaded Niosomes can be prepared by hand shaking method and ether injection method with Span 80 and cholesterol in the ratio of 1:1, 2:1, and 3:1. Preformulation studies and drug excipients compatibility studies was done initially and results directed the further course of formulation. Most of the vesicles are spherical in shape, the size range of the vesicles, fall in the narrow size range of 0.5-5 and 0.5-2.5 by hand shaking method and ether injection method respectively. A high % of Acyclovir can be encapsulated in the vesicles (75-84%) prepared by hand shaking method. Concentration of non-ionic surfactant such as Span 80 might influences the drug release pattern of all formulation. In vitro release of Acyclovir from niosomes was very slow when compared to the release from pure Acyclovir solution. Drug release studies showed that the niosomal preparation was stable at refrigeration temperature (40C). The vesicles prepared by hand shaking method were found to be larger in size as compared to vesicles prepared by ether injection method. Almost constant drug release was observed in all formulations indicating zero order release pattern.