Evaluation of the Properties of Encapsulated Stavudine Microparticulate Lipid-based Drug Delivery System in Immunocompromised Wistar Rats.

BACKGROUND: Lipid-based formulations have been confirmed to lower some side effects of drugs and can be tailor-made to offer sustained drug release of drugs with short half-life like stavudine. AIM: This study aimed to evaluate the immunomodulatory properties of stavudine-loaded solid lipid microparticles (SLMs) using immunocompromised Wistar rats. METHODS: The SLMs were formulated by the homogenization method. The optimized batches were used for further in vivo studies. The effect of formulation on the CD4 count and the haematological properties of immunocompromised Wistar rats were studied. RESULTS: The particle size range was 4 -8 µm, EE range was 85-93 % and maximum drug release was observed at 10 h. The CD4 cells increased from 115 ± 3.17 cell/mm3 at day zero to 495 ± 5.64 cell/mm3 at day 14 of treatment and 538 ± 6.31 cell/mm3 at day 21. The red blood cells increased from 2.64 ± 1.58 (x 106/mm3) at day zero to 6.96 ± 3.47 (x 106/mm3) at day 14 and 7.85 ± 3.64 (x 106/mm3) at day 21. PCV increased significantly (p < 0.05) to about 42-50 % at day 21 in the groups that received the SLMs formulations. White blood cells (WBC) also were 12 x 103/mm3, for SLM formulations, while the rats that received plain stavudine exhibited WBC of 9.6 x 103/mm3 at day 21. The histopathological studies revealed that oral stavudine-loaded SLMs had no significant damage to the kidney, liver, spleen and the brain of Wistar rats. CONCLUSION: The formulations exhibited significantly higher immunomodulatory properties than plain stavudine (p<0.05) and showed good properties for once daily oral administration and could be a better alternative to plain stavudine tablets for the management of patients living with HIV.

Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin.

The purpose of this study was to formulate and evaluate novel PEGylated solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of 15% w/w Phospholipon® 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was formulated and characterized by differential scanning calorimetry (DSC). SLMs were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic parameters determined. In vitro permeation of gentamicin from the SLMs through artificial membrane (0.22 µm pore size) was carried out using Franz's cell and phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation was performed using clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of size range 34.49 ± 2.56 to 53.52 ± 3.09 µm were obtained. The SLMs showed sustained drug permeation and exhibited time-dependent and capacity-limited bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, gave highest IZD against the test organisms and highest permeation flux (5.239 µg/cm(2).min) and permeation coefficient (1.781 × 10(-6)cm/min) within 420 min, while pure gentamicin gave the least. Preliminary in vivo pharmacokinetic studies also showed an AUC-24 of 1507 µg/h/ml for the optimized formulation, while that of oral drug solution was 678 µg/h/ml. This showed a 2.2-fold increase in the systemic bioavailability of gentamicin from the optimized formulation. PEGylated SRMS-based SLMs prepared with heterolipid from Irvingia gabonensis would likely offer a reliable delivery system for gentamicin.

Evaluation of dika wax-soybean oil-based artesunate-loaded lipospheres: in vitro-in vivo correlation studies.

OBJECTIVES: To formulate and evaluate artesunate-loaded lipospheres and study the in vitro-in vivo correlations (IV-IVC). MATERIALS AND METHODS: Lipospheres were formulated by melt homogenisation using structured lipid matrices consisting of (1:3 and 1:6) soybean oil and dika wax and were characterised in vitro and in vivo. RESULTS: The small angle X-ray diffraction (SAXD) results of the lipid matrices showed prominent reflection at 2θ = 2.49°, d = 3.55 Å while, wide angle X-ray diffraction (WAXD) showed prominent reflection at 2θ = 20.83°, d = 0.42 Å. Lipospheres had maximum encapsulation efficiency of 80%, showed no significant decrease in pH with time (p < 0.05), and had sustained release properties. The ratio of the area under the curve (AUC) of the lipospheres and the tablets gave bioavailability enhancement factor of 2.108. CONCLUSION: Artesunate-loaded lipospheres could be used orally or parenterally once daily, for the treatment of malaria.

Evaluation of the properties of Gongronema latifolium in phospholipon 90H based solid lipid microparticles (SLMs): an antidiabetic study.

CONTEXT: Gongronema latifolium Benth Hook, (Asclepiadaceae) is a tropical rainforest plant primarily used in traditional folk medicine in the treatment of malaria, diabetes, hypertension, and as laxative. OBJECTIVE: To study the antidiabetic properties of Gongronema latifolium-loaded solid lipid microparticles (SLMs). MATERIALS AND METHODS: The methanolic extract of Gongronema latifolium leaves were obtained and formulated into SLMs using lipid matrix comprising of fat from Capra hircus and Phospholipon® 90H. The SLMs were characterized in vitro by determining the particle size and morphology, pH stability studies, and encapsulation efficiency EE%. Also, the antidiabetic properties of the Gongronema latifolium-loaded SLMs were studied in alloxan-induced diabetic rats. RESULTS AND DISCUSSION: The results show that the particle size of G. latifolium-loaded SLMs was within an acceptable range for SLMs. Highest EE% of 68% was obtained for SLMs containing 5% G. latifolium (batch F3). The formulations remained stable with insignificant pH reduction over time (p < 0.05). Gongronema latifolium-loaded SLMs had mean percentage reduction in blood glucose of 76% at 2 h, 42.3% at 8 h, and 24.4% at 12 h, while the group that received the reference-glibenclamide had 82.6, 61.7, and 46.7% at 2, 8, and 12 h, respectively, after oral administration of all samples. Gongronema latifolium-loaded SLMs had blood glucose reduction significantly higher than the pure extract and the glibenclamide (p < 0.05) at the concentrations used. CONCLUSIONS: Gongronema latifolium-loaded SLMs exhibited a good hypoglycemic effect and could be used for the treatment of diabetes.

Nanovesicular carriers as alternative drug delivery systems: ethosomes in focus.

INTRODUCTION: The application of vesicular carrier formulations has generated promise of overcoming some problems associated with drug delivery arising from not only the physicochemical properties of the drug but also those of the biological barriers, such as the membrane linings of various body tissues and the skin. This review article discusses the importance of various vesicular carriers, namely liposomes, niosomes, transfersomes and ethosomes in drug delivery with greater emphasis on ethosomes. AREAS COVERED: The nature, mechanism of drug delivery, methods of preparation as well as characterization of vesicular carriers was discussed with a focus on ethosomes. An overview of their potential applications was provided with discussions on the future prospects and challenges of achieving enhanced drug delivery using ethosomes. EXPERT OPINION: Vesicular carriers offer controlled and sustained drug release, improved permeability and protection of the encapsulated bioactives. Ethosomes offer more efficient and enhanced bioavailability better than the older dosage forms owing to the high ethanol content. Ethosomes have potential applications in the development of nanomedicines, including phytomedicines, for the treatment of challenging diseases ravaging the world today. The future holds great prospects in the utilization of vesicular carriers, especially ethosomes, in overcoming peculiar problems of drug delivery.