No abstract

The development of in situ-gelling hydrogels that can enable prolonged protein release is increasingly important due to the emergence of a growing number of protein-based therapeutics. Herein, we describe a highthroughput strategy to fabricate, characterize, and subsequently optimize hydrazone-cross-linked in situ-gelling hydrogels for protein delivery. Hydrogels are fabricated using an automated high-throughput robot to mix a variety of thermoresponsive, nonthermoresponsive, charged, neutral, naturally sourced, and synthetic polymers functionalized with hydrazide or aldehyde groups, generating in situ-gelling hydrogels with well-defined compositions within a 96-well plate. High-throughput characterization strategies are subsequently developed to enable on-plate analysis of hydrogel swelling, mechanics, degradation, transparency, and protein (ovalbumin) release kinetics that yield results consistent with those collected using traditional bulk hydrogel analysis techniques. Dynamic regression and latent variable modeling are then applied to fit performance statistics to the collected data set; subsequently, numerical optimization is used to identify mixtures of precursor polymers that exhibit targeted combinations of minimal burst release, maximum total protein release, minimum release rate, and maximum transparency (the latter of particular relevance for ophthalmic protein delivery applications). Given the rapid throughput of the protocols developed (i.e., 126 hydrogels can be synthesized and screened in quadruplicate within hours), this approach offers particular promise for accelerating the identification of injectable hydrogel compositions relevant for both protein delivery as well as other biomedical applications for which clearly predefined materials properties are required.

No abstract

A simple one-pot synthesis and functionalization of HMSNs with COOH as a sustained and controlled release drug delivery system.

Magnetic, pH and temperature-sensitive, poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites with fluorescent properties were synthesized by free radical copolymerization-cross linking of NIPAM, N,N-dimethylaminoethyl methacrylate (DMAEMA) and 4-acrylamidofluorescein (AFA). The model anti-cancer drug, cisplatin (CDDP), was loaded into the resulted nanogel. For the production of CDDP-loaded nanocomposite, FeO magnetic nanoparticles (MNPs) and CDDP were loaded into the nanogel. Field-emission scanning electron microscopy (FE-SEM) indicated that the size of nanogel and CDDP-loaded nanocomposite were about 90 and 160 nm, respectively. The encapsulation efficiency of CCDP was found up to 65%. The loaded CCDP showed sustained thermal and pH-responsive drug release. A high level of drug release was observed under the conditions of low pH and high temperature. The lower critical solution temperature (LCST) of synthesized nanogel was about 40 °C. CDDP-loaded nanocomposite showed a volume phase transition from 282 to 128 nm at its LCST. Accordingly, in this study, the synthesized nanocomposite can be employed as a stimuli-responsive anti-cancer drug delivery system and the pH and temperature of solution have the potential to monitor the drug release.