PHARMACOKINETIC STUDIES OF IN-SITU LIPOSOMAL PREPARATION CONTAINING AMPHOTERICIN B COMPLEXED WITH DIFFERENT CHEMICALLY MODIFIED Β-Cyclodextrins

Abstract

The purpose of this study was to evaluate the influence of chemically modified beta-cyclodextrin (beta-CD) which could affect the in-vivo stabilization of liposomal preparation derived from proliposome entrapping inclusion complex of amphotericin B (AmB) with beta-CD. A series of liposomal AmB formulations with varying beta-CD i.e. Hydroxypropyl beta-CD (HPBCD) & Sulfo butyl ether beta-CD (SBEBCD) and lipid dose having similar AmB content (0.5 mg/kg) were compared with conventional liposomal amphotericin B (L-AmB) or free AmB in rats and their pharmacokinetic data were analyzed considering the varying volume of distribution with respect to the varying lipid concentration (65mg to 110mg) in blood. These results indicate that L-AmB entrapped inclusion complexes safely achieved higher Cmax (P < 0.05) & AUC (P < 0.02) and demonstrated saturable, nonlinear elimination from plasma via reticuloendothelial organ uptake at higher lipid level (>80mg) as compared with conventional L-AmB or free AmB. Furthermore in-vivo stabilization potential for liposomal preparation via AmB/ beta-Cyclodextrin inclusion complexes appeared to be in pattern of HPBCD < SBEBCD. It is concluded that the preparation of liposome derived from proliposome entrapping inclusion complex of amphotericinB (AmB) with beta-CD could serve an alternative approach to enhance the therapeutic window of AmB in clinical medicine.

Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes

“…Another example is the parenteral administration of melarsoprol (Table ). The AUC decreases by almost 50% when melarsoprol was given as an aqueous parenteral HPβCD solution compared with a solution in an equivolume mixture of propylene glycol, dimethyl sulfoxide and saline [33]. The authors propose that HPβCD delivers the drug very effectively to the biomembranes while the very poorly soluble drug dissolved in organic solvents precipitates upon parenteral administration, both of which affected the observed V D and t ½ of the drug after intravenous injection.…”

Local delivery polymer provides sustained antifungal activity of amphotericin B with reduced cytotoxicity

“…Cyclodextrin (CD) is a ring of 6, 7, or 8 glucose molecules with a hydrophilic exterior and slightly hydrophobic interior, sometimes used pharmacologically to solubilize hydrophobic drugs including AmB. 14,17,18 Importantly, liposomes containing AmB complexed with chemically modified β-cyclodextrin (βCD) achieved better area under the curve and maximum serum concentrations than liposomal AmB without βCD complexation. 17 In their work, Chakraborty and Naik hypothesized that the βCD–AmB complex slowed transfer of AmB from the liposome to the plasma and host tissues, causing the improved properties that were seen.…”

Study of immunological aspects of aspergillosis in mice and effect of polyene macrolide antibiotic (SJA-95) and IFN-γ: A possible role of IFN-γ as an adjunct in antifungal therapy

“…Preliminary studies on the antibiotic elicited promising antifungal activity in vitro against yeasts, filamentous fungi and clinical isolates and in vivo experiments [9]. Increased toxicity and lack of bioavailability of polyene antibiotics at the infected site have been major problems in antifungal treatment [10] necessitating administration of the liposomal incorporated drug to target more specifically to the sites of infection [11][12][13].…”