Impact of polyethylene glycol and polydopamine coatings on the performance of camptothecin-loaded liposomes for localised treatment of colorectal cancer

Management of colorectal cancer (CRC) remains a global healthcare challenge as current therapies are unable to offer optimal clinical efficacy and meet patient expectations. The oral route is particularly appealing for managing CRC due to its low invasiveness and direct access to affected areas, making it possible for localised action. However, different barriers oppose achieving proper drug concentration at tumour sites. In this work, the drug candidate camptothecin was incorporated into liposomes to overcome its poor solubility and pH instability, as well as to enhance drug distribution in the gastrointestinal tract. Two polymeric coatings were tested to improve liposome performance, namely 'standard' polyethylene glycol (PEG) and 'novel' polydopamine (PDA). Liposomes were characterized for physicochemical properties, in vitro drug release, mucus transport, in vitro intestinal permeability and anticancer activity using HCT 116 cell-based 2D and 3D (spheroids) models. Drug-loaded liposomes (130-157 nm) were successfully prepared and featured sustained drug release in intestinal fluids in a pH-independent manner. Drug release was slower in the case of PDA-coating and consistent with long-reaching colorectal drug delivery. Both polymers conferred sub-diffusive behaviour to liposomes in a mucus surrogate and allowed a mild increase (up to roughly 2.5-fold) in epithelial drug permeability as compared to free camptothecin. Anticancer activity was maintained or even increased for liposomal formulations. For instance, camptothecin-loaded, PDA-coated liposomes were over 2-fold more cytotoxic to HCT 116 cell spheroids than the free drug. Overall, proposed formulations, namely PDA-modified liposomes, present the potential to be used for localised treatment of CRC.Orally delivered therapeutics offer great promise for localized treatment of colorectal cancer. However, various natural barriers along the gastrointestinal tract need to be tackled to allow effective drug delivery to tumoral sites.