Advances in Micelle-based Drug Delivery: Cross-linked Systems

There are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.