Co-delivery of antibiotic and baicalein by using different polymeric nanoparticle cargos with enhanced synergistic antibacterial activity.

To evaluate the effect of polymer structures on their unique characteristics and antibacterial activity, this study focused on developing amphiphilic copolymers by using three different molecules through RAFT polymerization. Three amphiphilic copolymers, namely, PBMA-b-(PDMAEMA-r-PPEGMA) (BbDrE), (PBMA-r-PDMAEMA)-b-PPEGMA (BrDbE), and PBMA-r-PDMAEMA-r-PPEGMA (BrDrE), are successfully self-assembled into spherical or oval shaped nanoparticles in aqueous solution and remain stable in PBS, LB, and 10% FBS solutions for at least 3 days. The critical micelle concentrations are 0.012, 0.025, and 0.041 mg/mL for BbDrE, BrDbE, and BrDrE, respectively. The zeta potential values under pH 5.5 and pH 7.4 conditions are 3.18/0.19, 8.57/0.046, and 2.54/-0.69 mV for BbDrE, BrDbE, and BrDrE nanoparticles, respectively. The three copolymers with similar monomer compositions show similar molecular weight and thermostability. Baicalein (BA) and ciprofloxacin (CPX) are encapsulated into the three nanoparticles to obtain BbDrE@BA/CPX, BrDbE@BA/CPX, and BrDrE@BA/CPX nanocomposites, with LC values of 63.9/78.3, 63.9/74.7, and 55.3/64.8, respectively. The two drugs are released from the three drug-loaded nanocomposites with 60%-95% release in pH 5.5 over 24 h and 15%-30% release in pH 7.4. The drug-loaded nanocomposites show synergistic antibacterial activity than the naked drug (2-8 fold reduction for CPX) or single drug-loaded nanocomposites (4-8 fold reduction for CPX) against Pseudomonas aeruginosa and Staphylococcus aureus. The drug-loaded nanocomposites inhibit the formation of bacterial biofilms above their MIC values and eliminate bacterial biofilms observed by fluorescent microscope. Finally, the nanocomposites improve the healing of infection induced by P. aeruginosa and S. aureus on rat dermal wounds. These results indicate that antimicrobial agents with different structures could be an alternative treatment strategy for bacteria-induced infection.

Dynamical release nanospheres containing cell growth factor from biopolymer hydrogel via reversible covalent conjugation.

For practical adipose regeneration, the challenge is to dynamically deliver the key adipogenic insulin-like growth factors in hydrogels to induce adipogenesis. In order to achieve dynamic release, smart hydrogels to sense the change in the blood glucose concentration is required when glucose concentration increases. In this study, a heparin-based hydrogel has been developed for use in dynamic delivery of heparin nanospheres containing insulin-like growth factor. The gel scaffold was facilely prepared in physiological conditions by the formation of boronate-maltose ester cross-links between boronate and maltose groups of heparin derivatives. Due to its intrinsic glucose-sensitivity, the exposure of gel scaffold to glucose induces maltose functionalized nanospheres dissociation off hydrogel network and thereby could dynamically move into the microenvironment. The potential of the hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this dynamic hydrogel could support survival and proliferation of ASCs. This biocompatible coupling chemistry has the advantage that it introduces no potentially cytotoxic groups into injectable gel scaffolds formed and can create a more biomimetic microenvironment for drug and cell delivery, rendering them more suitable for potential in vivo biomedical applications. All these results indicate that this biocompatible gel scaffold can render the formulation of a therapeutically effective platform for diabetes treatment and adipose regeneration.