Intactness of Synthetic vs. Natural Polymeric Micelles in Physiological Conditions: A Comparative Review

Typical synthetic polymeric micelles are nano-sized core/shell structures of self-assembled aggregates of amphiphilic molecules. The hydrophilic "head" sections of the molecules form a shell in contact with water, whereas the hydrophobic "tails" are sequestered in the aggregate’s core, which has the potential to capture and protect water-insoluble drugs. However, these structures are shown to lose their integrity in body fluids due to dilution and protein interactions. The natural polymeric micelles (such as chitosan, alginate, collagen etc.) have attracted significant interest in recent years as drug delivery agents in the pharmaceutical field as they provide controlled release, drug targeting, hydrophobic active material solubilization, and high cell uptake efficiency due to their small size, with the added advantage of intrinsic biocompatibility and biodegradability, which is always a question with synthetic polymers. However, biopolymers in their natural form are not suitable for self-assembly, and they require assistance through the chemical modification of biopolymer molecules to obtain hydrophobic functional groups for self-assembly. However, recent studies have shown that the stability problem of synthetic polymeric micelles that encapsulate drugs physically still remains for natural polymeric micelles in the presence of proteins, even though they maintain their integrity with dilution in blood plasma, unlike synthetic polymeric micelles. This requires additional surface modifications to make the natural polymeric micelles protein resistant in the blood. Sometimes, the chemical modification of biopolymeric molecules is provided by the chemical bonding of hydrophobic drug molecules for self-assembly and to maintain the integrity of these types of micelles. However, this type of chemical bonding requires a detailed study on the efficiency of drug molecules that may be affected.