Development of a Temperature-Sensitive Composite Hydrogel for Drug Delivery Applications

Abstract

To develop materials with improved controllability and specificity, we have investigated composite hydrogels with temperature-sensitive properties using photo cross-linking. Specifically, our novel composite materials are composed of nanoparticles made of poly(N-isopropylacrylamide) (PNIPAAm), temperature-sensitive hydrogels, and a photo cross-linker, poly(ethylene glycol) diacrylate (PEGDA). PNIPAAm particles were synthesized by emulsion polymerization and by varying concentration of four main factors: monomers (N-isopropylacrylamide), cross-linkers (N,N'-methylenebisacrylamide), surfactants (sodium dodecyl sulfate, SDS), and initiators (potassium persulfate). We found that the surfactant, SDS, was the most important factor affecting the particle size using the factorial design analysis. Additionally, both nano- and micro-PNIPAAm particles had excellent loading efficiency (>80% of the incubated bovine serum albumin (BSA)), and their release kinetics expressed an initial burst effect followed by a sustained release over time. Furthermore, BSA-loaded PNIPAAm nanoparticles were used to form three-dimensional gel networks by means of a photocuring process using a photo cross-linker, PEGDA, and a photoinitiator, Irgacure-2959 (I-2959). Results from scanning electron microscopy and in vitro BSA release studies from these hydrogels demonstrated that PNIPAAm nanoparticles were embedded inside the PEG polymeric matrix and the composite material was able to release BSA in response to changes in temperature. These PNIPAAm nanoparticle hydrogel networks may have advantages in applications of controlled drug delivery systems because of their temperature sensitivity and their ability of in situ photopolymerization to localize at the specific region in the body.

Synthesis and characterization of PNIPAM/PS core/shell particles

“…Among all of the thermosensitive polymers, poly(N-isopropylacrylamide) (PNIPAM) is the most well known and profoundly studied one with a LCST $ 31-32 C. Polystyrene-based colloidal polymer particles have been widely utilized as carriers for bio-diagnostic applications. 1 The unique properties of PNIPAM inspired researchers to combine PNIPAM with polystyrene (PS) in areas such as biomedical 2 and bioseparations, 3 drug delivery, 4 catalysts, 5 and pollution control. 6 However, it is interesting to note that almost all of the research reported in the literature focused on synthesizing a PNIPAM shell around a PS core (or similar other polymeric materials), [7][8][9][10] although there are several studies describing the synthesis of a PNIPAM-based core and a PS shell.…”

Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

“…In situ polymerization is a method that can be employed to develop polymers that can withstand the harsh conditions of the gastric region in order to protect and deliver macromolecules through the oral route (20). In situ polymerization such as free radical and interfacial polymerizations are rapid and cross-linking density can be controlled to modulate drug release (21). The polymerization process of photopolymerization for instance can be undertaken at temperatures and pHs within physiological ranges (22).…”

One-step pipetting and assembly of encoded chemical-laden microparticles for high-throughput multiplexed bioassays

“…In other words, the ECMs are photopolymerized hydrogels with a unique code representing the type of chemical that is physically entrapped within the polymer matrix. The hydrogel microparticles can hold a sub-nanolitre volume of chemicals, which is much less than in other delivery methods of chemicals [10][11][12][13] , and these hydrogels are individually identifiable by their 2D graphical barcodes [14][15][16][17][18][19] . To prepare the ECM library, each chemical is loaded into a correspondingly encoded hydrogel, and these ECMs are stored in a shrunken and dried form.…”