Synthesis and Characterization of Degradable p(HEMA) Microgels: Use of Acid‐Labile Crosslinkers

Abstract

New divinyl-functionalized acetal-based crosslinkers were synthesized as building elements to form acid-labile microgel particles for controlled-release applications. The synthesized crosslinkers underwent hydrolysis at slightly acidic pHs in less than 1 h while they were stable at neutral pHs for longer times. HEMA was copolymerized with the crosslinkers via an inverse emulsion polymerization technique using a redox initiator system at room temperature to form crosslinked, colloidal p(HEMA) microgels. Microgels in diameters ranging from 150 to 475 nm with narrow distribution could be produced. The crosslinking density and the diameter of the microgels were found to be controlled by monomer/crosslinker feed ratio. The microgels demonstrated a pH-dependent cleavage behavior that mimicked the pH-dependent hydrolysis profile of the acid-labile crosslinkers. Model biomacromolecules, i.e., Rhodamine B-labeled dextran and BSA were efficiently loaded into the microgels. The release of the biomolecules from p(HEMA) microgels was also found to be controllable by the pH of the environment similar to the particle degradation. The protein released from the microgels was observed to retain its structural stability.

Core-crosslinked pH-sensitive degradable micelles: A promising approach to resolve the extracellular stability versus intracellular drug release dilemma

“…In particular, pH-responsive micelles have attracted great attention due to existence of mildly acidic pH in the tumor tissues as well as in the endo/lysosomal compartments of cells [26,27]. Over the past decade, different pH-responsive micelles have been developed based on acid-labile bonds such as ortho ester, hydrazone, cis-acotinyl, and acetal for enhanced intracellular drug release [28][29][30][31][32][33][34][35][36]. We recently reported that biodegradable micelles and polymersomes based on poly(ethylene glycol)-b-poly(mono-2,4,6-trimethoxy benzylidene-pentaerythritol carbonate) (PEG-b-PTMBPEC) block copolymers are prone to rapid hydrolysis thereby "actively" releasing drug under endo/lysosomal pH conditions [37,38].…”

Reconstitutable charged polymeric (PLGA)2-b-PEI micelles for gene therapeutics delivery

“…Many formulations made from liposomes or polymer-based systems exist as colloidal liquids, which are generally stable for short periods of time [32]. However, some polymer systems are designed to be gradually degradable by hydrolysis so long-term storage in liquid form is not a viable option for these types of systems [33]. In addition, many formulations can become unstable if kept in liquid form during long-term storage due to a variety of issues including degradation of the non-viral vector and/or drug [34], formation of insoluble aggregates [35], unwanted drug release [36], and loss of bioactivity [37].…”

Polymeric nucleic acid carriers: current issues and novel design approaches

“…Polymer-based colloidal formulations may be a viable option because polymeric vectors are generally prepared in a liquid form. However, polymers as liquid formulations may be gradually degraded [47, 48], and therapeutics may undergo unwanted release [49] with reduced bioactivity [50] during long-term storage. To overcome the stability limitations of colloidal formulations, an alternative is a powder formulation prepared from liquid product, followed by buffer reconstitution when necessary.…”