Preparation of polymersomes from synthesized hyaluronic acid-graft-poly(ε-caprolactone) copolymers for drug delivery to the brain

The application of amphiphilic block copolymer for drug delivery has received immense attention in recent years. Polymersomes are favorable types of polymeric systems that can load different molecules and their structures and functional properties can be decorated for various drug-releasing platforms. Here, we represent a hyaluronic acid (HA) and polycaprolactone (PCL)-based amphiphilic block copolymer that can be assembled as polymersomes via the solvent substitution strategy. HA-graft-PCL copolymers were synthesized by a novel method, through the formation of an amide bond between the N-terminal amino acid of PCL and the carboxyl (–COOH) group in HA. Following the assemblage of copolymers, nanopolymersomes were coated with polysorbate-80 (P80) to target blood–brain barrier receptors. To determine the functional capacity of this vehicle, celecoxib (COXI) was loaded into nanopolymersomes. Then, particle size distribution, encapsulation efficiency, zeta potential, and polydispersity index were improved to 95%, 120 ± 10 nm, −21 mV, and ≤0.2, respectively. The P80-COXI-NPOL (P80 coated-COXI loaded-Nanopolymersomes) exhibited up to 72 h of sustained drug release in phosphate-buffered saline. Besides, the release profile revealed a biphasic pattern containing initial anomalous release (n = 0.63) in the first 9 h, followed by a linear pattern in 9–72 h (zero-order model). Overall, through targeted delivery of the encapsulated drug (COXI), these nanopolymersomes provide a passive targeting system to spot P80 receptors on the blood–brain barrier.