Characterization and efficacy evaluation of protein nano-carrier based drug delivery systems for therapeutic applications

Drug delivery system (DDS)promises to solve a number of issues associated with conventional therapeutic agents, including their poor bioavailability, lack of targeting capability, nonspecific distribution, systemic toxicity and low therapeutic index. Naturally occurring bio-molecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in fabrication of DDS because of their biocompatibility and biodegradability. Moreover, due to the presence of reactive groups protein-based nanoparticles can be surface functionalised with the target specific ligands.Common methods available for the preparation of protein nanoparticles are desolvation, emulsification, high pressure homogenization, etc. Major disadvantages with these methods are use of organic solvent and removal of organic oil from the nanoparticle solution. Further, the most common stabilizing agent used in previous studies is glutaraldehyde which can cause toxicity. Therefore, there is a need to develop greener methods that can overcome toxicity associated with excipients. The proposed thesis is thus aimed to develop physical and chemical methods of preparing nano-carrier from protein sources namely albumin and gelatin and to evaluate them as DDS. Well established anti-inflammatory/anticancer drugs such as Curcumin, Doxorubicin (Dox) and Irinotecan (IRI) were chosen as payload to study the role of physico-chemical properties like surface modification, size and hydrophobicity of protein nanoparticles in controlling the release and pharmacokinetic behavior of the entrapped drug. Finally, attempts were also made to evaluate the optimized nano formulations of curcumin, Dox and IRI for various therapeutic applications using murine models. The presentation will give brief overview of results pertaining to thesis objectives