Therapeutic and hemolytic evaluation of in-situ liposomal preparation containing amphotericin - beta complexed with different chemically modified beta - cyclodextrins.
OBJECTIVE
The objective of this study was to evaluate therapeutic and haemolytic effects of liposomal preparation derived from proliposome entrapping inclusion complex of amphotericin B (AmB) with the chemically modified beta-cyclodextrin (beta-CD).


METHODS
a series of liposomal AmB formulations with varying beta-CD i.e. Hydroxy propyl beta-CD (HPBCD) and Sulfo butyl ether beta-CD (SBEBCD) having similar AmB content (0.5 mg/kg) were prepared and their effect compared with conventional liposomal amphotericin B (L-AmB) and free AmB on erythrocyte lysis and antifungals activity in experimental aspergillosis- and Cryptococcosis- mice model in-vivo.


RESULTS
the liposomal AmB - HPBCD and AmB - SBEBCD found to be 6 times less toxic than free AmB or conventional liposomal AmB. Experimental findings indicate that infected animals treated with L-AmB entrapped inclusion complexes significantly reduced CFU values (fungal counts), whereas infected animals treated with conventional liposome or free AmB showed insignificant reduction in CFU. A marked increase in the percent survival was observed in the case of animals treated with liposomal AmB formulation (HPBCD/SBEBCD). Furthermore, the in-vitro toxicity (haemolysis) of the proliposome-based liposomal vesicles (PBLV) entrapped AmB-SBEBCD/HPBCD at 37 degrees C was approx. 50% at maximum of the conventional liposomal AmB at a dose of 118 microg/ml as measured after 1 hr. incubation.


CONCLUSIONS
the results of these experiments permitted us to conclude that the stabilization of liposome derived from proliposome entrapping inclusion complex of amphotericin B (AmB) with beta-CD could serve an alternative approach to enhance the therapeutic window of AmB in clinical medicine.
Chakraborty
K K
KK
Research and Development Division, Hindustan Antibiotics Ltd., Pimpri, Pune, India. kkchakrabor@yahoo.com
Naik
S R
SR
D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D003505:Cyclodextrins / Q000737:chemistry*; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000935:Antifungal Agents; D003505:Cyclodextrins; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B