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Polymers containing thiol‐reactive maleimide groups on their side chains have been synthesized by utilization of a novel methacrylate monomer containing a masked maleimide. Diels‐Alder reaction between furan and maleimide was adapted for the protection of the reactive maleimide double bond prior to polymerization. AIBN initiated free radical polymerization was utilized for synthesis of copolymers containing masked maleimide groups. No unmasking of the maleimide group was evident under the polymerization conditions. The maleimide groups in the side chain of the polymers were unmasked into their reactive form by utilization of retro Diels‐Alder reaction. This cycloreversion was monitored by thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC), and 1H and 13C NMR spectroscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4545–4551, 2007

On the occasion of the 10th anniversary of click chemistry FOCUS REVIEWSAbstract: Hydrogels are crosslinked polymeric materials that play a vital role in many biomedical areas such as drug delivery, sensor technology, and tissue engineering. Increasing demand of these materials for such advanced applications has necessitated the development of hydrogels with complex chemical compositions such as incorporating small molecules and biomolecules that provide the functional attributes. This Focus Review highlights the tremendous impact of click chemistry on the design, synthesis, and functionalization of hydrogels. The high efficiency and fidelity of the click reactions have enabled rapid and modular synthesis of hydrogels with near-ideal network structures. Efficient incorporation of biomolecular building blocks, such as peptide sequences either during or after the fabrication of hydrogels, have been achieved through various click reactions. Utilization of these efficient reactions has led to the fabrication of many stimuli-responsive or 'smart' hydrogels in recent years.

Polymerization-induced self-assembly (PISA) is a facile one-pot synthetic technique for preparing polymeric nanoparticles with different sizes and shapes for application in a variety of fields including nanomedicine. However, the in vivo biodistribution of nanoparticles obtained by PISA still remains unclear. To address this knowledge gap, we report the synthesis, cytotoxicity, and biodistribution in an in vivo tumor-bearing mouse model of polystyrene micelles with various sizes and polystyrene filomicelles with different lengths prepared by PISA. First, a library of nanoparticles was prepared comprised of poly(glycidyl methacrylate)-b-poly(oligo(ethylene glycol) methyl ether methacrylate)-b-polystyrene polymers, and their size and morphology were tuned by varying the polystyrene block length without affecting the surface chemistry. The H) ethanolamine, and a biodistribution study was carried out in nude mice bearing HT1080 tumor xenografts 48 h after intravenous delivery. In this model, we found that small spherical polystyrene core nanoparticles with a PEG corona (diameter 21 nm) have the highest tumor accumulation when compared to the larger spherical nanoparticles (diameter 33 nm) or rodlike (diameter 37 nm, contour length 350-500 nm) or wormlike counterparts (diameter 45 nm, contour length 1-2 μm). This finding has provided critical information on the biodistribution of polystyrene core nanoparticles with a PEG corona of different sizes and shapes prepared by the PISA technique and will inform their use in medical applications.

The steady increase in antimicrobial resistance in different pathogens requires the development of alternative treatment strategies next to the oral delivery of antibiotics. A photothermally activated platform based on reduced graphene oxide (rGO)-embedded polymeric nanofiber mats for on-demand release of antibiotics upon irradiation in the near-infrared is fabricated. Cross-linked hydrophilic nanofibers, obtained by electrospinning a mixture of poly(acrylic acid) (PAA) and rGO, show excellent stability in aqueous media. Importantly, these PAA@ rGO nanofiber mats exhibit controlled photothermal heating upon irradiation at 980 nm. Nanofiber mats are efficiently loaded with antibiotics through simple immersion into corresponding antibiotics solutions. Whereas passive diffusion based release at room temperature is extremely low, photothermal activation results in increased release within few minutes, with release rates tunable through power density of the applied irradiation. The large difference over passive and active release, as well as the controlled turn-on of release allows regulation of the dosage of the antibiotics, as evidenced by the inhibition of planktonic bacteria growth. Treatment of superficial skin infections with the antibiotic-loaded nanofiber mats show efficient wound healing of the infected site. Facile fabrication and implementation of these photothermally active nanofiber mats makes this novel platform adaptable for on-demand delivery of various therapeutic agents.

Functionalizable hydrogels are of great interest as three-dimensional (3D) scaffolds for cell growth and tissue engineering. The ability to covalently immobilize biologically relevant molecules with accurate control of their density within the hydrogel matrix is highly desirable. Dendron−polymer conjugates prepared via Huisgen type “click” reaction provides a unique precursor for reactive hydrogels. A family of dendron−polymer conjugates were prepared by coupling second- and third-generation alkyne appended polyester dendrons with linear poly(ethylene glycol) diazides, PEG2K and PEG6K. Controlled cross-linking of alkyne-functionalized dendron−polymer−dendron conjugates with a hydrophilic diazide provides hydrogels with gelation efficiencies greater than 80%. Excess leftover alkynes can be used to functionalize these hydrogels as desired. Fine tuning of degree of cross-linking and functionalization is demonstrated by immobilization of streptavidin.

tothermally triggered on-demand insulin release from reduced graphene oxide modified hydrogels. Journal of Controlled Release, Elsevier, 2017Elsevier, , 246, pp.164-173. 10.1016Elsevier, /j.jconrel.2016 Abstract.On-demand delivery of therapeutics plays an essential role in simplifying and improving patient care. The high loading capacity of reduced graphene oxide (rGO) for drugs has made this matrix of particular interest for its hybridization with therapeutics. In this work, we describe the formulation of rGO impregnated poly(ethylene glycol) dimethacrylate based hydrogels (PEGDMA-rGO) and their efficient loading with insulin. Near-infrared (NIR) light induced heating of the PEGDMA-rGO hydrogels allows for highly efficient insulin release. Most importantly, we validate that the NIR irradiation of the hydrogel has no effect on the biological and metabolic activities of the released insulin. The ease of insulin loading/reloading makes this photothermally triggered release strategy of interest for diabetic patients. Additionally, the rGO-based protein releasing platform fabricated here can be expanded towards 'on demand' release of various other therapeutically relevant biomolecules. The table of contents entry: Poly(ethylene glycol) based hydrogels impregnated with rGO allow efficient loading and 'on demand' photothermal release of insulin while preserving its biological and metabolic activity.

Poly(ethylene glycol) methacrylate-based hydrogels containing thiol reactive maleimide functional groups have been synthesized using a novel Diels-Alder cycloaddition/cycloreversion-based strategy. Masked maleimide groups are directly incorporated into the hydrogel matrix during the gelation process by utilization of a furan protected maleimide containing methacrylate monomer. During the polymerization, the thermal deprotection of the maleimide groups in some of the monomer results in the formation of an in situ cross-linker that results in gelation. After gelation, the protected maleimide groups can be activated to their reactive forms via a thermal cycloreversion step. The efficiency of the gel formation, maleimide incorporation, and functionalization of the hydrogel were investigated. These reactive maleimide group embedded hydrogels can be efficiently derivatized with thiol containing molecules such as a fluorescent dye, BodipyC10SH. Thiolated biotin derivatives were covalently attached to these hydrogels under mild, reagent-free conditions. It was found that the extent of immobilization of FITC-streptavidin onto these biotinylated gels can be tailored by varying the density of maleimide groups in the parent hydrogels.