Characterization and Evaluation of Rapamycin-Loaded Nano-Micelle Ophthalmic Solution

Abstract

Rapamycin-loaded nano-micelle ophthalmic solution (RAPA-NM) offers a promising application for preventing corneal allograft rejection; however, RAPA-NM has not yet been fully characterized. This study aimed to evaluate the physicochemical properties, biocompatibility, and underlying mechanism of RAPA-NM in inhibiting corneal allograft rejection. An optimized RAPA-NM was successfully prepared using a polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol (PVCL-PVA-PEG) graft copolymer as the excipient at a PVCL-PVA-PEG/RAPA weight ratio of 18:1. This formulation exhibited high encapsulation efficiency (99.25 ± 0.55%), small micelle size (64.42 ± 1.18 nm), uniform size distribution (polydispersity index = 0.076 ± 0.016), and a zeta potential of 1.67 ± 0.93 mV. The storage stability test showed that RAPA-NM could be stored steadily for 12 weeks. RAPA-NM also displayed satisfactory cytocompatibility and high membrane permeability. Moreover, topical administration of RAPA-NM could effectively prevent corneal allograft rejection. Mechanistically, a transcriptomic analysis revealed that several immune- and inflammation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the downregulated genes in the RAPA-NM-treated allografts compared with the rejected allogenic corneal grafts. Taken together, these findings highlight the potential of RAPA-NM in treating corneal allograft rejection and other ocular inflammatory diseases.

Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives

“…These biomimetic hydrogels undergo reversible phase transitions in response to changes in temperature, leading to triggered drug release. By tuning the lower critical solution temperature (LCST) of thermoresponsive polymers, nanocarriers can be designed to release drugs upon exposure to physiological or external heat stimuli, offering on-demand drug delivery with enhanced spatial and temporal control [ 304 ]. Heating-induced drug release systems are an innovative and versatile approach in nanomedicine, utilizing various materials that respond to thermal stimuli to achieve controlled and targeted therapeutic delivery.…”

Nanotechnology-based ocular drug delivery systems: recent advances and future prospects

“…Nanotechnology refers to treating structures at the nanoscale level, which ranges in size from 1 to 100 nm and is proportionally comparable to peptide drugs [ 17 ]. Their basic physicochemical properties, such as visual appearance, size, zeta potential, refractive index, pH, retention, viscosity, osmolality, biodegradability, surface charge, hydrophobicity and biodegradability are closely related to their therapeutic efficacy in the ocular pathological environment [ 23 , 305 ]. Therefore, we characterized nanocarriers' physicochemical and biological properties to provide new ideas for better design of effective novel delivery systems.…”

Exosomal miR‐181d‐5p Derived from Rapamycin‐Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6

“…[38,46,[55][56][57][58] Moreover, our previous findings underscored the excellent anti-rejection effect of Rapa nano-micelle ophthalmic solution through MDSCs. [47,48] Thus, we speculated that Rapa-Exo delayed the allograft rejection better than exosomes derived from untreated MDSCs (Nor-Exo). To test this assumption, the anti-rejection effect of exosomes with different origins was investigated in a well-established murine corneal transplantation model (Figure 2A).…”

“…[43][44][45][46] However, the application and mechanisms underlying exosome-based therapy in allograft rejection have not been fully addressed. Using the murine corneal transplantation model, we revealed an anti-rejection effect of rapamycin (Rapa) nano-micelle, [47,48] mechanistically associated with the enhancement of MDSCs ' immunosuppressive function. [47] Some studies highlighted the potential applications of MDSC-derived EVs in preclinical autoimmune/inflammatory disease models, especially in rheumatoid arthritis, [49,50] inflammatory bowel disease, [51] and autoimmune alopecia areata.…”