Pilosebaceous targeting by isotretenoin-loaded invasomal gel for the treatment of eosinophilic pustular folliculitis: optimization, efficacy and cellular analysis.

CONTEXT: Eosinophilic pustular folliculitis is a secondary symptom associated with HIV infection appears as levels of CD4 lymphocyte cells and T4 lymphocyte cell. Isotretinoin, an analog of vitamin A (retinoid) alters the DNA transcription mechanism and interferes in the process of DNA formation. It also inhibits the eosinophilic chemotactic factors present in sebaceous lipids and in the stratum corneum of patients suffering from this ailment. OBJECTIVE: The present research was aimed to formulate isotretenoin-loaded invasomal gel to deliver and target the drug to pilosebaceous follicular unit. METHODS: Nine invasomal formulations (F1-F9) were prepared applying 32 factorial designs and characterized. RESULTS: Formulation F9 was selected as optimized formulation due to optimum results and highest %CDP of 85.94 ± 1.86% in 8 h. Transmission electron microscopy (TEM) suggested uniformity in vesicles shape and size in F9 and developed as invasomal gel (IG). LIMITATIONS: Clinical phase-I, phase-II, and phase-III studies will be required before using on human patients. CONCLUSION: Confocal laser scanning microscopy (CLSM) validates that IG successfully reaches the pilosebaceous follicular unit and further studied on cell line (SZ-95) exhibited IC50 of ≤8 (25 µM of isotretenoin). Cell cycle analysis confirmed IG arrested the cell growth up to 82% with insignificant difference to pure isotretenion.

Hemoglobin guided nanocarrier for specific delivery of amphotericin B to Leishmania infected macrophage.

Leishmania donovani being an intracellular parasite poses many challenges against the attempted chemotherapy. After the resistance towards the first line of antileishmanial drug, Amphotericin B has been the treatment of choice against visceral leishmaniasis, a fatal tropical disease. However, unfavorable toxicity profile, severe side effects, prolonged parenteral administration procedure limits the use of Amphotericin B. Lack of available specific delivery system also makes this drug unsafe for the prolonged use. In this current study, a chitosan-chondroitin sulfate based nanodelivery vehicle has been introduced. Hemoglobin has been attached on the surface of the delivery system for specifically targeting the leishmania infected macrophage taking the advantage of Leishmania being highly auxotrophic for heme. This cheap and biodegradable delivery vehicle has improved the toxicity profile and lowered LD50 value of the drug significantly compared to traditional way of its direct administration.