Development and evaluation of Panax notoginseng saponins contained in an in situ pHtriggered gelling system for sustained ocular posterior segment drug delivery

Objective:This study aimed to lay the foundation for the research on Panax notoginseng saponins(PNS)in pH-sensitive in situ gel and the development and improvement of related preparations.Methods:We used Carbopol■940,a commonly used pH-sensitive polymer,and the thickener hydroxypropyl methylcellulose(HPMC E4M)as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS.In addition,formula optimization was performed by assessing gelling capability with the results of in vitro release studies.In vitro(corneal permeation,rheological,and stability)and in vivo(ocular irritation and preliminary pharmacokinetics in the vitreous)studies were also performed.Results:The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug,making it an ideal ocular delivery system for improving posterior ocular bioavailability.Conclusions:This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations.It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.

Cryo-self-assembled silk fibroin sponge as a biodegradable platform for enzyme-responsive delivery of exosomes

Although advances in protein assembly preparation have provided a new platform for drug delivery during tissue engineering,achieving long-term controlled exosome delivery remains a significant challenge.Diffusion-dominated exosome release using protein hydrogels results in burst release of exosomes.Here,a fibroin-based cryo-sponge was developed to provide controlled exosome release.Fibroin chains can self-assemble into silk I structures under ice-cold conditions when annealed above the glass transition temperature.Exosome release is enzyme-responsive,with rates primarily determined by enzymatic degradation of the scaffolds.In vivo experiments have demonstrated that exosomes remain in undigested sponge material for two months,superior to their retention in fibrin glue,a commonly used biomaterial in clinical practice.Fibroin cryo-sponges were implanted subcutaneously in nude mice.The exosome-containing sponge group exhibited better neovascularization and tissue ingrowth effects,demonstrating the efficacy of this exosome-encapsulating strategy by realizing sustained release and maintaining exosome bioactivity.These silk fibroin cryo-sponges containing exosomes provide a new platform for future studies of exosome therapy.