Liposomal drug delivery system from laboratory to clinic.
The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, Fungisome) drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India. We have therefore devoted a section of our review to the relative costs of our product and those of other commercially available products. This patient-worthy formulation is safe, efficacious and cheaper than the commercially available formulation of liposomal amphotericin B. The product has been patented and technology transferred to a pharmaceutical company for marketing. Results of postmarketing study also document safety and efficacy as observed in premarketing studies. A brief review of this work is provided here.
Kshirsagar
N A
NA
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Parel, India. dcpkem@vsnl.com
Pandya
S K
SK
Kirodian
G B
GB
Sanath
S
S
D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008081:Liposomes
D000935:Antifungal Agents; D008081:Liposomes; D000666:Amphotericin B