Montmorillonite-loaded solid lipid nanoparticles with good biocompatibility, using Betaxolol hydrochloride as model drug, were prepared by the melt-emulsion sonication and low temperature-solidification methods and drug bioavailability was significantly improved in this paper for the first time to application to the eye. The appropriate physical characteristics were showed, such as the mean particle size, Zeta potential, osmotic pressure, pH values, entrapping efficiency (EE%) and drug content (DC%), all showed well suited for possible ocular application. In vitro release experiment indicated that this novel system could continuously release 57.83% drugs within 12 h owing to the dual drug controlled-release effect that was achieved by ion-exchange feature of montmorillonite and structure of solid lipid nanoparticles. Low irritability and good compatibility of nanoparticles were proved by both CAM-TBS test and cytotoxicity experiment. We first discovered from the results of Rose Bengal experiment that the hydrophilicity of the drug-loaded nanoparticles surface was increased during the loading and releasing of the hydrophilic drug, which could contribute to prolong the ocular surface retention time of drug in the biological interface membrane of tear-film/cornea. The results of in vivo pharmacokinetic and pharmacodynamics studies further confirmed that increased hydrophilicity of nanoparticles surface help to improve the bioavailability of the drug and reduce intraocular pressure during administration. The results suggested this novel drug delivery system could be potentially used as an in situ drug controlled-release system for ophthalmic delivery to enhance the bioavailability and efficacy.
Traditional antibiotics are often ineffective against biofilm-associated infections, and biofilm-induced macrophage immune evasion directly halts the wound healing process. Disrupting biofilms and regulating macrophage immune functions are critical to improving wound healing. In this study, we synthesized g-C 3 N 4 with peroxidase (POD) enzyme activity via thermal polymerization and copper alginate microspheres (CAM) via gas cutting. These were co-encapsulated into GelMA hydrogels to form a functionalized wound repair system (GelMA/CAM@g-C 3 N 4 ) with both anti-biofilm and local immune microenvironment remodeling capabilities. In vitro, this system exhibited excellent biocompatibility and promoted endothelial cell migration, vascular formation, and CD31 expression. It also polarized macrophages toward the M1 phenotype, restoring their pro-inflammatory functions, upregulating inflammatory cytokines (IL-1, IL-6, TNF-α), and inhibiting Staphylococcus aureus and Escherichia coli . In vivo, the system suppressed S. aureus growth, promoted angiogenesis and collagen deposition, and reshaped the pathological microenvironment to achieve wound repair and regeneration. Conclusions: This system offers a new therapeutic strategy for chronic infectious wounds.
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