Stimuli-responsive polypeptide nanogels loaded with α1-antitrypsin for inhibition of inflammatory mediator trypsin

A new type of hydrophilic, biocompatible, and biodegradable polypeptide nanogel depots loaded with natural serine protease inhibitor α1-antitrypsin (AAT) was applied for inhibition of inflammatory mediator trypsin. Further, poly[N5-(2-hydroxyethyl)-L-glutamine-ran-N5-propargyl-L-glutamine-ran-N5-(6-aminohexyl)-L-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-L-glutamine] (PHEG-Tyr) and Nα-L-Lysine-grafted α,β-poly[(2-propyne)-D,L-aspartamide-ran-(2-hydroxyethyl)-DL-aspartamide-ran-(2-(4-hydroxyphenyl)ethyl)-DL-aspartamide] (Nα-Lys-NG) nanogels were prepared by HRP/H2O2-mediated crosslinking in inverse miniemulsions with pH and temperature-stimuli responsive behavior confirmed by dynamic light scattering and zeta potential measurements. The loading capacity of PHEG-Tyr and Nα-Lys-NG nanogels and their release profiles were firstly optimized with bovine serum albumin (BSA) and then used for loading and release of AAT. PHEG-Tyr and Nα-Lys-NG nanogels showed different loading capacities for AAT with the maximum (20 %) achieved with Nα-Lys-NG nanogel. In both cases, the nanogels depots demonstrated a burst release of AAT during 6 h, which could be favorable for quick inhibition of trypsin. A consequent pilot in vitro inhibition study revealed that both PHEG-Tyr and Nα-Lys-NG nanogels loaded with AAT successfully inhibited the enzymatic activity of trypsin. Furthermore, the inhibitory efficiency of the AAT-loaded nanogels was higher than that of AAT itself, indicating that the negatively charged polypeptide nanogels enhance the inhibitory function of AAT loaded in the nanogel depots.

Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering

The versatile natural polymer, collagen, has gained vast attention in biomedicine. Due to its biocompatibility, biodegradability, weak antigenicity, biomimetics and well-known safety profile, it is widely used as a drug, protein and gene carrier, and as a scaffold matrix in tissue engineering. Nanoparticles develop favorable chemical and physical properties such as increased drug half-life, improved hydrophobic drug solubility and controlled and targeted drug release. Their reduced toxicity, controllable characteristics of scaffolds and stimuli-responsive behavior make them suitable in regenerative medicine and tissue engineering. Collagen associates and absorbs nanoparticles leading to significant impacts on their biological functioning in any biofluid. This review will discuss collagen nanoparticle preparation methods and their applications and developments in drug delivery systems and tissue engineering.

Effective End-Group Modification of Star-Shaped PNVCL from Xanthate to Trithiocarbonate Avoiding Chemical Crosslinking

In this study, six-arm star-shaped poly(N-vinylcaprolactam) (PNVCL) polymers prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization were subjected to aminolysis reaction using hexylamine. Chemically crosslinked gels or highly end-functionalized star polymers can be obtained depending mainly on the type of solvent used during the transformation of the RAFT functional group. An increase in the viscosity of the solution was observed when the aminolysis was carried out in THF. In contrast, when the reaction was conducted in dichloromethane, chain-end thiol (PNVCL)6 star polymers could be obtained. Moreover, when purified (PNVCL-SH)6 star polymers are in contact with THF, the gelation occurs in just a few minutes, with an obvious increase in viscosity, to form physical gels that become chemically crosslinked gels after 12 h. Interestingly, when purified (PNVCL-SH)6 star polymers were stirred in distilled water, even at high aqueous solution concentration (40 mg/mL), there was no increase in the viscosity or gelation, and no evident gels were observed. The analysis of the hydrodynamic diameter (Dh) by dynamic light scattering (DLS) did not detect quantifiable change even after 4 days of stirring in water. On the other hand, the thiol groups in the (PNVCL-SH)6 star polymers were easily transformed into trithiocarbonate groups by addition of CS2 followed by benzyl bromide as demonstrated by UV-Vis spectroscopical analysis and GPC. After the modification, the (PNVCL)6 star polymers exhibit an intense yellow color typical of the absorption band of trithiocarbonate group at 308 nm. To further demonstrate the highly effective new trithiocarbonate end-functionality, the PNVCL polymers were successfully chain extended with N-isopropylacrylamide (NIPAM) to form six-arm star-shaped PNIPAM-b-PNVCL block copolymers. Moreover, the terminal thiol end-functionality in the (PNVCL-SH)6 star polymers was linked via disulfide bond formation to l-cysteine to further demonstrate its reactivity. Zeta potential analysis shows the pH-responsive behavior of these star polymers due to l-cysteine end-functionalization. By this using methodology and properly selecting the solvent, various environment-sensitive star polymers with different end-groups could be easily accessible.

Photo-Responsive Hydrogel Mns with Interlocking Control for Easy Extraction in Sustained Ocular Drug Delivery

Microneedle arrays provide a minimally invasive platform for ocular drug delivery. Self-adhesive microneedle arrays, which incorporate barb-like locking features, have been developed secure the array in place without using any adhesive. However, these locking features present a challenge on removing the microneedle array when the drug delivery is completed. In this study, we demonstrated a photo-responsive hydrogel microneedle array that can self-adhere to the application site upon swelling and can deswell for easy removal when illuminated with light. The photo-responsive hydrogel microneedle arrays were made by a mixture of polyvinyl alcohol and spiropyran-conjugated N-isopropylacrylamide (NIPPAM). Experimental results show a significant decrease in extraction force after the microneedle of 20% spiropyran-conjugated NIPPAM was illuminated with light for 15 minutes. At the same time, the width of the interlocking feature also deswelled by 20% due to the photo-responsive behavior. However, the addition of the spiropyran-conjugated NIPPAM also weakens the mechanical properties of the microneedle and thus an increase in insertion force.

Polymer for Internal Hydrophobization of Cement-Based Materials: Design, Synthesis, and Properties

A series of novel comb-like poly(butyl acrylate)-g-poly(dimethylaminoethyl methacrylate) (PBA-g-PDMAEMA) with different side chain lengths were designed and successfully synthesized by the “first main chain then side chain” method. Infrared Spectroscopy (IR), 1H Nuclear Magnetic Resonance (1H NMR), and gel permeation chromatography (GPC) were used for structural confirmation and molecular weight characterization. This polymer exhibited responsive behavior from hydrophilicity to hydrophobicity under the alkaline environment of cement-based materials, with the contact angle of 105.6°, a decreased evaporation rate, and a hydrophile–lipophile balance (HLB) value. A significant internal hydrophobic effect on cement mortar was shown in the water absorption rate, which decreased by 75.2%, and a dry shrinkage-reducing rate of more than 30%. Furthermore, this polymer can effectively slow the exothermic rate, reduce the heat release, and delay the exothermic peak of cement hydration. It was interesting that these properties showed a direct correlation with the side chain length of the comb polymer. The aims of this study are to provide a new avenue to synthesize polymers with the spontaneous hydrophilicity–hydrophobicity transition in the cement system, achieving excellent internal hydrophobicity of cement-based materials, and to offer a promising alternative to resist external erosion for improving the durability and service life of cement-based materials.