mPEG-CS-modified flexible liposomes-reinforced thermosensitive sol-gel reversible hydrogels for ocular delivery of multiple drugs with enhanced synergism.

Non-invasive drug delivery offers a safe treatment while improving patient compliance. However, due to the particular physiological structure of the ocular, long-term retention and sustained drug release of the drug delivery system is crucial. Herein, this study aimed to design mPEG-CS-modified flexible liposomes-reinforced thermosensitive sol-gel reversible hydrogels (mPEG-CS-FL-TSG) for the delivery of astragaloside IV (AS-IV) and tetramethylpyrazine (TMP) to treat age-related macular degeneration. In vitro biological properties of mPEG-CS-FL and mPEG-CS-FL-TSG showed that they could be successfully taken up by ARPE-19 cells, and the uptake rate of mPEG-CS-FL-TSG was higher. Not only that, the release rate of mPEG-CS-FL-TSG was slower. More significantly, the results showed that the cytotoxicity of mPEG-CS-FL-TSG was lower than that of mPEG-CS-FL. In vivo result revealed that the drug delivery system could prominently enhance the ocular bioavailability of AS-IV and TMP, which is the enhanced synergism of well-permeable liposome and slow-releasing hydrogel. In summary, the mPEG-CS-FL-TSG can compensate for the short retention time and sudden release of liposome, as well as the low drug penetration of hydrogel, in order to show great promise in the non-invasive delivery of multiple drugs for the treatment of posterior ocular diseases.

Potential in exosome-based targeted nano-drugs and delivery vehicles for posterior ocular disease treatment: from barriers to therapeutic application.

Posterior ocular disease, a disease that accounts for 55% of all ocular diseases, can contribute to permanent vision loss if left without treatment. Due to the special structure of the eye, various obstacles make it difficult for drugs to reach lesions in the posterior ocular segment. Therefore, the development of highly permeable targeted drugs and delivery systems is particularly important. Exosomes are a class of extracellular vesicles at 30-150 nm, which are secreted by various cells, tissues, and body fluids. They carry various signaling molecules, thus endowing them with certain physiological functions. In this review, we describe the ocular barriers and the biogenesis, isolation, and engineering of exosomes, as exosomes not only have pharmacological effects but also are good nanocarriers with targeted properties. Moreover, their biocompatibility and immunogenicity are better than synthetic nanocarriers. Most importantly, they may have the ability to pass through the blood-eye barrier. Thus, they may be developed as both targeted nano-drugs and nano-delivery vehicles for the treatment of posterior ocular diseases. We focus on the current status and potential application of exosomes as targeted nano-drugs and nano-delivery vehicles in posterior ocular diseases.

Nano-composite system of traditional Chinese medicine for ocular applications: molecular docking and three-dimensional modeling insight for intelligent drug evaluation.

The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10-5 mol/m3 and 6.37×10-6 mol/m3. In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations.

A strategy based on gene sequencing and molecular docking for analysis and prediction of bioactive peptides in Shuxuetong injection.

Peptides are a class of protein fragments with relatively high biological activity and intense specificity, which play crucial role in the treatment of Shuxuetong injection (SXT). However, the extraordinary complexity of Chinese medicinal formulates and the lack of systematic identification methods are primary challenges for study of pharmacodynamic peptides. In addition, infinitesimal peptides contents further hinder the identification and structural characterization of polypeptide by traditional means. In this paper, we described a strategy that LC-MS combined with molecular docking to systematically illustrate the peptide components of SXT. The key to this research was used of gene sequencing to establish a SXT protein database to further achieve the separation and enrichment of chemical methods. Moreover, the ADRA2A, PAR4 and DRD3 were precisely docked with the identified peptides. The result indicated that 12 compounds had stable binding ability and were speculated to be the latent bioactive monomers for the treatment of stroke. Additionally, 12 peptides were verified by cell-based experiment. The results showed that only YLKTT could indeed protect astrocytes from oxygen glucose deprivation/reoxygenation (OGD/R). The YLKTT showed higher activity than the others in vitro. It might be a completely new compound that has never been reported before, providing the basis for further research and a new paradigm for stroke.