Formulation and Characterization of Photosensitive Liposomes of Anticancer Drugs

Abstract

Liposomes are tiny phospholipid bilayer vesicles intended to prepare for the safe and effective drug delivery. The prime purpose to formulate liposomes is to deliver potent and toxic drugs to improve their therapeutic efficiency. The flexibility of modification in liposomes make them a useful drug delivery system in various field like protein /drug delivery, controlled delivery, antiviral therapy, tumour therapy, gene delivery, vaccine delivery, cosmetics and dermatology and others. However, there are some stability issues and incomplete drug release at target site are attached with liposomes. In order to achieve maximum or appropriate therapeutic response drug in required quantity should be available to the target cells in the disease like cancer. Hence, considering the example of cancer, delivery of drug with liposomes to the site should be released in therapeutic concentration. For this purpose external stimuli can be used effectively to enhance the release of drug from liposomes. These approaches can use temperature, pH and light. The use of light to stimulate the release of encapsulated compounds from liposomes is attractive, because spatial and temporal delivery of the radiation can be possible to control. In the present study, to eradicate non therapeutic and toxic effects associated anticancer drugs like 5-fluorouracil (5-FU) and γ-Oryzanol (OZ) encapsulated reversed phase evaporation vesicles (REVs) carrying photoactive destabilization agent ketoprofen (KP) in the lipid bilayer were formulated. Effect of UV radiation activation of liposomal membrane incorporated KP on the destabilization of the liposome bilayer and the release of encapsulated drugs was investigated. 5-FU loaded photosensitive liposomes and conventional liposomes were formulated and characterized. Lipid and cholesterol molar ratio was optimized on the basis of particle size and entrapment efficiency (% EE). Size of formulated photosensitive liposome was found 122 nm and with maximum % EE of 45.4 %. Further study included in vitro release from photosensitive liposomes in presence of light. Photosensitive liposomes showed remarkable release of 5-FU compared to the conventional liposomes. Permeation study was performed using tape stripping method. Photosensitive liposomes showed remarkable increase in permeation when compared to free drug and conventional liposomes. SRB assay was performed to find the GI50 values of prepared formulations and photosensitive liposome showed improved cytotoxicity with GI50 value of 24.0 compared to free drug and conventional liposomes. Formulated was tested for storage stability and found stable by protected from light at 40 C. These results were supported by in vivo study using animal model. Healthy swiss albino mice were used and DMBA was used to induce skin cancer. Animals were treated with photosensitive and conventional liposomes to find their efficacy against induced cancer. Different antioxidant stress parameters were estimated and significant (p<0.05) improvement was observed with photosensitive liposomes treated animals.