Novel thermogelling dispersions of polymer nanoparticles for controlled protein release

Abstract

A novel poly(oligo(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) ethyl ether methacrylate)/ poly(acrylic acid) interpenetrating network (IPN) nanoparticle was synthesized. The temperature-responsive properties of the IPN nanoparticles were investigated by dynamic light scattering method. Atomic force microscopic images confirm the homogenous and mono-disperse morphology of the IPN nanoparticles. Both visual observation and viscosity testing demonstrated that the IPN nanoparticles exhibit thermogelling properties at body temperature, 37°C. Subsequent studies verified that such temperature sensitive properties of IPN nanoparticles allow their ease of injection and then slow release of model proteins, both in vitro and in vivo. Histological analysis showed that our IPN implants exerted minimal inflammation following subcutaneous implantation. Our results support that, by simply mixing with proteins of interest, the novel IPN nanoparticles can be used to form in situ thermogelling devices for controlled protein release.

Preparation of a novel injectable in situ-gelling nanoparticle with applications in controlled protein release and cancer cell entrapment

“…Synthesis of P(MEO 2 MA-co-OEGMA 300 -co-AAc) (PMOA) hydrogel nanoparticles A series of hydrogel nanoparticles were synthesized via a free radical precipitation polymerization method. 18 In brief, MEO 2 MA, OEGMA 300 , AAc, SDS, EGDMA and DI water were mixed in a 500 mL round bottle ask. The mixture was heated to 70 C in a water bath under nitrogen purging.…”

“…Furthermore, the building blocks (particles) can be employed as carriers of growth factors or bioactive molecules to deliver them in a controlled manner for guiding differentiation of stem cells. 13,17,18 Among these particle-based thermogelling systems, poly(N-isopropylacrylamide) (PNIPAM)-based microgels are the most studied and have been widely explored as in situ forming scaffolds for use in tissue engineering. 13,17,[19][20][21][22][23][24][25][26] PNIPAM polymer has a lower critical solution temperature (LCST) at near to physiological temperature therefore, PNIPAM-based microgels can be used for reversible cell adhesion or detachment and for triggered release of therapeutics.…”

“…27 The monomer of PNIPAM, N-isopropylacrylamide (NIPAM) is carcinogenic as well as the byproducts are neurotoxic, perhaps generated by hydrolysis of PNIPAM. 18 To overcome these concerns, a series of thermosensitive polymers or nanoparticles based on oligo(ethylene glycol) methacrylate (OEGMA) with different ethylene glycol chain lengths have been developed. [28][29][30][31] By copolymerization of OEGMA monomers with different length of ethylene glycol chain, the as-prepared nanoparticles have a wide range of LCST, similar to those of PNIPAM or PEG-based hydrogels.…”

Development and Characterization of Stimulus-Sensitive Nano/Microparticles for Medical Applications

“…Also, thermoresponsive and biocompatible interpenetrating network (IPN) NPs were prepared using poly(oligo (ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) ethyl ether methacrylate)-poly(acrylic acid). The particles showed temperature-and pH-dependent properties by gelling at 37 C only at pH 7 while remaining in liquid form in pH 4 at body temperature [52].…”

Non-invasive Characterization of Immune Responses to Biomedical Implants

“…Quantitative assessment of overall tissue responses necessitates analyses of many sections throughout the samples. 5, 16,33,77,105,115 Even with automation in sample preparation and basic staining, it would easily take a few weeks to process all samples from a study. Second, histological analyses require isolation of tissues from sacrificed animals.…”