Camptothecin-loaded Surface-modified Nanostructured Lipid Carriers Consisting of L-Cysteine- and L-Cystine-derived Lipids: Physicochemical Characterization and In Vitro Evaluation.

Abstract

Camptothecin (CPT) is a potent chemotherapeutic agent used in the treatment of colorectal, breast, ovarian, colon, and stomach cancers. However, its clinical application has been significantly restricted due to several drawbacks, including poor water solubility, nonselective toxicity, drug resistance, and inherent instability. To address some of these challenges and to enhance the stability, solubility, and biological efficacy of CPT, in this work, we have attempted to explore nanoparticulate delivery strategies using nanostructured lipid carriers (NLCs) for the targeted delivery of CPT. We have employed L-cysteine- and L-cystine-derived lipids, C₁₂-cys-C₁₂ and [C₁₂-cys]₂, along with isopropyl palmitate, as a co-liquid lipid to produce surface-modified NLCs. L-cystine was incorporated into the lipid structure in order to exploit its redox-sensitive disulfide (S─S) bond for stimuli-responsive delivery of CPT. Sulfur-containing L-cysteine and its oxidized form L-cystine containing S─S bond is expected to enhance anticancer drug delivery by offering improved therapeutic efficacy and biocompatibility over conventional lipids. This was confirmed by the glutathione (GSH) assay. The biocompatibility of NLC formulations was determined by in vitro MTT assay. It has been shown that compared to free CPT and cysteinelated NLC-CPT, the cystinelated NLC-CPT is more effective in killing both human hepatoma (HuH7) and colon carcinoma (Caco-2) cells.