Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs.

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.

Solubilization of chitosan in biologically relevant solvents by a low-temperature solvent-exchange method for developing biocompatible chitosan materials.

Chitosan has great potential for biomedical applications. However, the intractable solubility of chitosan is a major bottleneck hampering its utilization. In this work, we report a low-temperature solvent-exchange method to solubilize chitosan in biologically relevant solvents (bio-solvents) including water, salines, and cell culture media. Chitosan was firstly dissolved in ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate (EMIM Ac). The chitosan/IL solution was then dialyzed against bio-solvents at 4 °C, during which a solvent exchange process took place. At the end of 24 h dialysis, aqueous chitosan pseudosolutions formed. Low temperature is found to be crucial for efficient solubilization of chitosan during the solvent exchange process. Increasing temperature to 50 °C leads to the formation of solid chitosan hydrogel. Chitosan in the water-based pseudosolution presents as positively charged particles. The pseudosolution shows a high positive zeta potential of about +52.6 mV and good colloidal stability. The water-based pseudosolutions with different amounts of chitosan contents exhibit the rheological features of weak liquid gels. By using these pseudosolutions, the fabrication of various chitosan materials is realized readily. Both chitosan pseudosolution and its downstream products are highly biocompatible. In this strategy, using IL as a solvent-medium and processing a low-temperature solvent exchange are the two key parameters to solubilize chitosan.

Biofabrication of poly(l-lactide-co-ε-caprolactone)/silk fibroin scaffold for the application as superb anti-calcification tissue engineered prosthetic valve.

In this study, electrospun scaffolds were fabricated by blending poly(l-lactide-co-ε-caprolactone) (PLCL) and silk fibroin (SF) with different ratios, and further the feasibility of electrospun PLCL/SF scaffolds were evaluated for application of tissue engineered heart valve (TEHV). Scanning electron microscopy (SEM) results showed that the surface of PLCL/SF electrospun scaffolds was smooth and uniform while the mechanical properties were appropriate as valve prosthesis. In vitro cytocompatibility evaluation results demonstrated that all of the PLCL/SF electrospun scaffolds were cytocompatible and valvular interstitial cells (VICs) cultured on PLCL/SF scaffolds of 80/20 & 70/30 ratios exhibited the best cytocompatibility. The in vitro osteogenic differentiation of VICs including alkaline phosphatase (ALP) activity and quantitative polymerase chain reaction (qPCR) assays indicated that PLCL/SF scaffolds of 80/20 & 90/10 ratios behaved better anti-calcification ability. In the in vivo calcification evaluation model of rat subdermal implantation, PLCL/SF scaffolds of 80/20 & 90/10 ratios presented better anti-calcification ability, which was consistent with the in vitro results. Moreover, PLCL/SF scaffolds of 80/20 & 70/30 ratios showed significantly enhanced cell infiltration and M2 macrophage with higher CD206+/CD68+ ratio. Collectively, our data demonstrated that electrospun scaffolds with the PLCL/SF ratio of 80/20 hold great potential as TEHV materials.

Injectable Multicomponent Biomimetic Gel Composed of Inter-Crosslinked Dendrimeric and Mesoporous Silica Nanoparticles Exhibits Highly Tunable Elasticity and Dual Drug Release Capacity.

There is a growing need for cartilage defect grafts that are structurally adaptable to possess multifaceted functions to promote bone regeneration, sustain medication efficacy, and preferably remain injectable but solidify quickly upon injection. In this work, we developed an injectable multicomponent biomimetic gel (MBG) by integrating polyamidoamine dendrimer G3 (G3), mesoporous silica nanoparticles (MSNs), and dendrimer-templated silver nanoparticles (G3-Ag) into a well-defined cross-linked network. MBGs composed of one particulate component (G3 alone), i.e., MBG-1, two particulate components (G3 and MSN-NH2), i.e., MBG-2, and three particulate components (G3, MSN-NH2, and G3-Ag), i.e., MBG-3, were prepared by inter-cross-linking dendrimeric and mesoporous silica nanoparticles with poly(ethylene glycol) diglycidyl ether (PEG-DGE, Mn = 2000 g/mol) via the facile amine-epoxy click reaction. The water-soluble antibiotic isoniazid was loaded to the cross-linked PEG network, whereas the hydrophobic antibiotic rifampicin was encapsulated into mesoporous MSNs. Our studies revealed that elasticity and mechanical strengths could be modulated and enhanced significantly with the inclusion of MSNs and silver nanoparticles. Isoniazid was released rapidly while rifampicin was released over an extended period of time. In addition, MBGs showed injectability, high swelling capacity, structural stability, and cytocompatibility. Taken together, MBGs have shown structural features that allow for the development of injectable gel grafts with the ability to promote cartilage defect repair and offer antibiotic medication benefits.