Chang Liu,Qi Lan,Wei He,Changlu Nie,Chunjuan Zhang,Tonghua Xu,Tongying Jiang,Siling Wang
The purpose of the study was to design a novel octa-arginine (R8) modified lipid emulsion (LE) system for the ocular delivery of the lipophilic drug disulfiram (DSF). The influence of the particle size of the lipid emulsions and the presence of R8 on corneal permeation was studied. DSF-loaded lipid emulsions with different particle sizes (DSF-LE1, DSF-LE2, DSF-LE3) and DSF-loaded lipid emulsions modified with R8 (DSF-LE1-R8 and DSF-LE2-R8) were prepared. The Zeta potential of the lipid emulsions was changed from negative to a positive value after modification of R8. The mucoadhesion of different preparations was investigated, and DSF-LE1-R8 was found to produce the strongest mucoadhesion. The in vitro corneal penetration study and in vivo ocular distribution study showed that the R8 modified lipid emulsion (DSF-LE1-R8) with a nano particle size, exhibited the highest permeability and the largest amount of DDC distributed in ocular issues. Coumarin-6 labelled LE1-R8 displayed more homogeneous fluorescence with the deeper penetration into the cornea compared with other preparations at various times. Confocal laser scanning microscopy showed that, in addition to paracellular routes, LE-R8 could also transport across the corneal epithelium by transcellular routes as a result of increased uptake due to the R8 modification. Furthermore, the anti-cataract effect was evaluated and it was found that DSF-LE1-R8 exhibited a marked anti-cataract effect. Therefore, the lipid emulsions with nano-sized particles and modification of R8 were proposed as a potential ocular delivery system to improve the corneal penetration and ocular delivery of DSF.
Xueling Long,Siyi Li,Yuxiang Ma,Yuting Cao,Shaoping Sun
Transdermal delivery is considered as a promising convenient and painless approach for the delivery of insulin. In this study, an amphiphilic peptide derivative of oleic acid modified octaarginine (R8-OA) and a photothermal nanomaterial of hyaluronic acid modified CuS (CuS-HA) were successfully synthesized. Using both materials as carriers, CuS-HA enveloped R8-OA@insulin nanocomplexes (HERNCs) were prepared. In vitro studies demonstrated that R8-OA could chemically enhance the penetration of insulin through the stratum corneum. In vivo laser activation studies suggested that CuS-HA in HERNCs could ablate the stratum corneum, thus facilitating the insulin penetration through physical enhancement. The hypoglycemic effect study revealed that blood glucose level in diabetic mice decreased to 42.3% within 4 h, and the value was maintained at 75.1% after 24 h. These results underscored the potential of the enveloped nanocomplexes for enhanced transdermal delivery of insulin.
Nimodipine is the primary clinical drug used to treat cerebral vasospasm following subarachnoid hemorrhage. Currently, tablets have low bioavailability when taken orally, and injections contain ethanol. Therefore, we investigated a new method of nimodipine administration, namely, nasoencephalic administration. Nasal administration of nimodipine was carried out by attaching the cell-penetrating peptide octa-arginine (R8) to liposomes of nimodipine and incorporating it into a temperature-sensitive in situ gel. The prepared liposomes and gels underwent separate evaluations for in vitro characterization. In vitro release exhibited a significant slow-release effect. In vitro toad maxillary cilia model, RPMI 2650 cytotoxicity, and in vivo SD rat pathological histotoxicity experiments showed that all the dosage from the groups had no significant toxicity to toad maxillary cilia, RPMI 2650 cells, and SD rat tissues and organs, and the cilia continued to oscillate up to 694 ± 10.15 min, with the survival rate of the cells being above 85%. A transwell nasal mucosa cell model and an isolated porcine nasal mucosa model were established, and the results showed that the osmolality of the R8-modified nimodipine liposomal gel to nasal mucosal cells and isolated porcine nasal mucosa was 30.41 ± 2.14 and 65.9 ± 7.34 μg/mL, respectively, which was significantly higher than that of the NM-Solution and PEGylated nimodipine liposome gel groups. Animal fluorescence imaging studies revealed that the R8-modified nimodipine liposomal gel displayed increased brain fluorescence intensity compared to the normal liposomal gel. Pharmacokinetic results showed that after transnasal administration, the AUC(0–∞) of the R8-modified nimodipine liposomal gel was 11.662 ± 1.97 μg·mL–1, which was significantly higher than that of the plain nimodipine liposomal gel (5.499 ± 2.89 μg·mL–1). Brain-targeting experiments showed that the brain-targeting efficiencies of the PEGylated nimodipine liposome gel and R8-modified PEGylated nimodipine liposome gels were 20.44 and 33.45, respectively, suggesting that R8/PEG/Lip-NM-TSG significantly increased the brain-targeting of the drug.
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