We describe the development and evaluation of a hybrid lipopolymeric system comprising carboxymethyl chitosan (CMC), covalently tethered to phosphatidylethanolamine units on the surface of lipid nanovesicles, for oral delivery of paclitaxel. The bioploymer is intended to act as a blanket, thereby shielding the drug from harsh gastrointestinal conditions, whereas the lipid nanovesicle ensures high encapsulation efficiency of paclitaxel and its passive targeting to tumor. CMC-tethered nanovesicles (LN-C-PTX) in the size range of 200-300 nm improved the gastrointestinal resistance and mucoadhesion properties as compared with unmodified lipid nanovesicles (LN-PTX). Conjugation of CMC did not compromise the cytotoxic potential of paclitaxel yet facilitated the interaction and uptake of the nanovesicles by murine melanoma (B16F10) cells through an ATP-dependent process. CMC-conjugated nanovesicles, upon oral administration in rats, improved the plasma concentration profile of paclitaxel, with 1.5 fold increase in its bioavailability and 5.5 folds increase in elimination half life in comparison with Taxol. We also found that CMC in addition to providing a gastric resistant coating also imparted stealth character to the nanovesicles, thereby reducing their reticuloendothelial system (RES)-mediated uptake by liver and spleen and bypassing the need for PEGylation. In vivo efficacy in subcutaneous model of B16F10 showed significantly improved tumor growth inhibition and survival with CMC-tethered nanovesicles as compared with unmodified nanovesicles, both administered orally. LN-C-PTX exhibited therapeutic efficacy comparable to Taxol and Abraxane and also showed reduced toxicity and improved survival. Overall, these results suggest the therapeutic potential of CMC tethered nanovesicles as a platform for oral administration of paclitaxel and also unravel the ability of CMC to impart stealth character to the nanoparticles, thereby preventing their RES clearance.

No abstract

Every living organism comprises of lipids as basic building blocks in addition to other components. Utilizing these lipids for pharmaceutical and biomedical applications can overcome biocompatibility and biodegradability issues. A well known example is liposomes (lipids arranged in lamellar structures), but other than that there are additional unique mesophasic structures of lipids formed as a result of lipid polymorphisms, which include cubic-, hexagonal- or sponge-phase structures. These structures provide the advantages of stability and production feasibility compared with liposomes. Cubosomes, which exist in a cubic structure, have improved stability, bioadhesivity and biocompatibility. Hexagonal phases or hexosomes exhibit hexagonal arrangements and can encapsulate different drugs with high stability. Lipids also forms tube-like structures known as tubules and ribbons that are also utilized in different biomedical applications, especially in tissue engineering. Immune stimulating complexes are nanocage-like structures formed as a result of interactions of lipid, antigen and Quillaja saponin. These lipidic mesophasic structures have been utilized for gene, vaccine and drug delivery. This article addresses lipid self-assembled supramolecular nanostructures, including cubosomes, hexosomes, tubules, ribbons, cochleates, lipoplexes and immune stimulating complexes and their biomedical applications.

No abstract

No abstract