Artificial neural network for optimizing the formulation of curcumin-loaded liposomes from statistically designed experiments.

Curcumin is a primary polyphenol of the rhizomatous perennial plant called Curcuma Longa. Curcumin interferes favorably with the cellular events that take place in the inflammatory and proliferative stages of wound healing, hence its importance in skin regeneration and wound healing. Curcumin is however lipophilic, and this must be considered in the choice of its drug delivery system. Liposomes are spherical vesicles with bi-lipid layers. Liposomes can encapsulate both lipophilic and hydrophilic drugs, hence their suitability as an ideal drug delivery system for curcumin. There is, nevertheless, a tendency for liposomes to be unstable and have low encapsulation efficiency if it is not formulated properly. Formulation optimization of curcumin-loaded liposomes was studied by the application of artificial neural network (ANN) to improve encapsulation efficiency and flux of the liposomes. The input factors selected for optimization of the formulation were sonication time, hydration volume, and lipid/curcumin ratio. The response variables were encapsulation efficiency and flux. The maximum encapsulation efficiency and flux were obtained using lipid/curcumin ratio of 4.35, sonicator time of 15 min, and hydration volume of 25 mL. The maximum encapsulation efficiency and flux predicted were 100% and 51.23 µg/cm2/h, respectively. The experimental values were 99.934% and 51.229 µg/cm2/h, respectively. Curcumin-loaded liposome formulation is a promising drug delivery system in the pharmaceutical industry when formulated using optimized parameters derived from ANN statistically designed models.

Mucoadhesive Microspheres of Maraviroc and Tenofovir Designed for Pre-Exposure Prophylaxis of HIV-1: An in vitro Assessment of the Effect on Vaginal Lactic Acid Bacteria Microflora.

PURPOSE: To formulate and evaluate microspheres of the antiretroviral drugs maraviroc and tenofovir intended for a candidate vaginal microbicide and assess its effect on the vaginal lactic acid bacteria microflora. METHODS: Ionic gelation technique was used to formulate maraviroc and tenofovir microspheres with subsequent characterization. The effect of varying concentrations of the polymer, crosslinking agent and the curing time on the outcome variables viz: particle size, mucoadhesion and encapsulation efficiency were investigated. Lactic acid bacteria were isolated from the vagina of healthy women using standard microbiologic methods. The analysis of their 16S rRNA sequence data identified Lactobacillus fermentum and Enterococcus faecalis strains which were assigned GenBank accession numbers. The efficacy of the microspheres on HIV-1BaL strain was evaluated using TZM-bl indicator cells. RESULTS: The optimal maraviroc and tenofovir microspheres had particle sizes of (434.82 µm and 456.18 µm), mucoadhesion of (93.3% and 90%) and encapsulation efficiency (92.80% and 78.9%) respectively. Maraviroc release kinetics followed a zero-order model and tenofovir was released via Higuchi model. The assay of a 1 mg/mL suspension of the microspheres on the strains of Lactobacillus fermentum and Enterococcus faecalis showed a viability of 93.9% and 89.7%, respectively. There was a statistically significant difference between the mean absorbance readings of the test agent and that of the positive control (P = 0.001). The microspheres elicited a progressive decline in HIV infectivity until at a concentration of 1 µg/mL. CONCLUSION: The antiretroviral drugs loaded in the microspheres, had good mucoadhesion which is a potential for prolonged residence time in the vagina. The antiretroviral drugs were adequately released from the microspheres and showed efficacy against the HIV-1 BaL virus strain. There was no significant disruption in the growth of the lactic acid bacteria which constitute valuable bacteria microflora of the vagina.

Encapsulation of Andrographolide in poly(lactide-co-glycolide) Nanoparticles: Formulation Optimization and in vitro Efficacy Studies.

Andrographolide is a potential chemopreventive and chemotherapeutic agent that suffers from poor aqueous solubility. Encapsulation in poly(lactide-co-glycolide) (PLGA) nanoparticles can overcome solubility issues and enable sustained release of the drug, resulting in improved therapeutic efficacy. In this study, andrographolide was encapsulated in PLGA nanoparticles via emulsion solvent evaporation technique. Effect of various formulation parameters including polymer composition, polymer molecular weight, polymer to drug ratio, surfactant concentration and the organic solvent used on nanoparticle properties were investigated. A selected formulation was used to determine the effect of encapsulation in nanoparticles on andrographolide's in vitro anticancer efficacy. Nanoparticles formulated using a polymer with 85:15 lactide to glycolide ratio and ethyl acetate as the organic solvent were found to be optimal based on average hydrodynamic particle size (135 ± 4 nm) and drug loading (2.6 ± 0.6%w/w). This formulation demonstrated sustained release of andrographolide over 48 h and demonstrated significantly greater in vitro anticancer efficacy compared to free drug in a metastatic breast cancer cell line. These results suggest that additional, more in-depth efficacy studies are warranted for the nanoparticle formulation of andrographolide.