Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.

Amphotericin B, a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis, though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability. Thus, to alleviate the toxicity and to improve oral bioavailability, an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B (AmbiOnp) was reported earlier by our group. In this investigation, we report the predominant formation of nontoxic superaggregated form of amphotericin B, resulting from the probe sonication-assisted nanoprecipitation technique. The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions. Further, in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7.812 µg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 ng/mL achieved with that of marketed formulation (Fungizone®) given intravenously establishing efficacy of AmbiOnp. In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies. Further, the formulations were found to be stable under refrigeration condition over a period of 3 months.

Comparative in vitro and in vivo evaluation of lipid based nanocarriers of Huperzine A.

The purpose of the present investigation was to explore feasibility of nanocarrier based transdermal delivery of Huperzine A (HupA) for the treatment of Alzheimer's disease. For this investigation, microemulsion (ME), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were formulated and characterized for physicochemical parameters. The pseudo-ternary phase diagrams for microemulsion region were developed using generally recognized as safe (GRAS) excipients. The SLNs and NLCs were prepared by microemulsion template technique. These nanodispersions were formulated into gels for transdermal application and evaluated for various physicochemical parameters. In vitro permeation profiles in rat skin exhibited zero-order kinetics. HupA loaded ME exhibited superior permeation than NLCs followed by SLNs and cumulative amount permeated after 24h was found to be 147.68±9.42 µg/cm(2), 129.11±32.76 µg/cm(2) and 10.74±0.68 µg/cm(2), respectively. Furthermore, optimized gels were subjected to primary skin irritation testing over a period of 48 h and were found to be safe for skin application. In vivo efficacy tested in scopolamine induced amnesia model indicated significant improvement in cognitive function in mice group treated with developed nanocarrier based formulations as compared to the control group.

AmbiOnp: solid lipid nanoparticles of amphotericin B for oral administration.

Amphotericin B is the most effective gold standard drug against various fungal infections, especially in second line treatment of leishmaniasis. However, its usefulness is limited due to severe nephrotoxicity, which may lead to kidney failure. Due to its poor oral bioavailability, it is often administered parenterally to patients suffering from systemic fungal infection or visceral leishmaniasis (kala azar). In this investigation, solid lipid nanoparticles were formulated for oral administration of Amphotericin B. For this purpose, novel microemulsion based nanoprecipitation technique was employed. The influence of process variables such as sonication and dialysis time was studied. The optimized formulation was characterized for parameters such as particle size, polydispersity index, zeta potential, drug content and entrapment efficiency. The pH stability of the developed Amphotericin B solid lipid nanoparticles (AmbiOnp) at pH 1.2, 4, 6.8 values demonstrated enhanced protection of entrapped Amphotericin B. Further, single dose acute toxicity study established the safety of AmbiOnp for oral administration. In vivo pharmacokinetic studies revealed increase in % relative bioavailability of AmbiOnp in comparison to the plain drug. Additionally, the t1/2 of encapsulated Amphotericin B was significantly greater than that of plain drug, indicating the controlled release of Amphotericin B from AmbiOnp. Overall, the developed formulation; AmbiOnp was found to be successful in oral delivery of Amphotericin B.