RESUMO
Uveitis is an ocular illness that if not treated properly can lead to a total loss of vision. In this study, we evaluated the utility of HA-coated Dexamethasone-sodium-phosphate (DEX)-chitosan nanoparticles (CSNPs) coated with hyaluronic acid (HA) as a sustained ocular delivery vehicle for the treatment of endotoxin-induced-uveitis (EIU) in rabbits. The CSNPs were characterized for particle size, zeta potential, polydispersity, surface morphology, and physicochemical properties. Drug encapsulation, in vitro drug release, and transcorneal permeation were also evaluated. Finally, eye irritation, ocular pharmacokinetics, and pharmacodynamics were in vivo. The CSNPs ranged from 310.4 nm and 379.3 nm pre-(uncoated) and post-lyophilization (with HA-coated), respectively. The zeta potentials were +32 mV (uncoated) and -5 mV (HA-uncoated), while polydispersity was 0.178-0.427. Drug encapsulation and loading in the CSNPs were 73.56% and 6.94% (uncoated) and 71.07% and 5.54% (HA-coated), respectively. The in vitro DEX release over 12 h was 77.1% from the HA-coated and 74.2% from the uncoated NPs. The physicochemical properties of the CSNPs were stable over a 3-month period when stored at 25 °C. Around a 10-fold increased transcorneal-flux and permeability of DEX was found with HA-CSNPs compared to the DEX-aqueous solution (DEX-AqS), and the eye-irritation experiment indicated its ocular safety. After the ocular application of the CSNPs, DEX was detected in the aqueous humor (AH) till 24 h. The area under the concentrations curve (AUC0-24h) for DEX from the CSNPs was 1.87-fold (uncoated) and 2.36-fold (HA-coated) higher than DEX-AqS. The half-life (t1/2) of DEX from the uncoated and HA-coated NPs was 2.49-and 3.36-fold higher, and the ocular MRT0-inf was 2.47- and 3.15-fold greater, than that of DEX-AqS, respectively. The EIU rabbit model showed increased levels of MPO, TNF-α, and IL-6 in AH. Topical DEX-loaded CSNPs reduced MPO, TNF-α, and IL-6 levels as well as inhibited NF-κB expression. Our findings demonstrate that the DEX-CSNPs platform has improved the delivery properties and, hence, the promising anti-inflammatory effects on EIU in rabbits.
RESUMO
In total, nine TPGS-b-PCL copolymers were synthesized employing distinct TPGS analogues (TPGS 2000, 3500, and 5000). In these copolymers, the length of the PCL chain varied according to the TPGS to PCL molecular weight ratio (1:1, 1:2, and 1:3). The formulation optimization was done by optimizing the drug to polymer ratio, encapsulation efficiency, drug loading, micelle diameter, and polydispersity index (PDI). TPGS3500-b-PCL7000 copolymer (TPGS to PCL ratio 1:2) with drug to polymer ratio 1:30 showed the best percentage encapsulation (63.50 ± 0.45 %) and drug loading (2.05 ± 0.07). The optimal micelle (CHR-M) diameter and PDI were determined to be 94.57 ± 13.40 nm and 0.16 ± 0.02, respectively. CHR-M showed slow release when compared with alcoholic solution of chrysin. Approximately 70.70 ± 6.4 % drug was released in 72 h. The CHR-M demonstrated considerably greater absorption in Hep G2 cells, which confirmed the reliability of the micellar carrier. The MTT assay results showed that the IC50 values for CHR-M were much lower after 24 and 48 h when compared to free chrysin. Therefore, CHR-M may be a viable carrier for active chrysin targeting with improved anticancer potential. Also, it could be a better alternative for the currently available treatment of hepatocellular carcinoma.
RESUMO
AIM: Diabetic (type-2) is a metabolic disease characterized by increased blood glucose level from the normal level. In the present study, apigenin (AG) loaded lipid vesicles (bilosomes: BIL) was prepared, optimized and evaluated for the oral therapeutic efficacy. EXPERIMENTAL: AG-BIL was prepared by a thin-film evaporation method using cholesterol, span 60 and sodium deoxycholate. The prepared formulation was optimized by 3-factor and 3-level Box-Behnken design using particle size, entrapment efficiency and drug release as a response. The selected formulation further evaluated for ex-vivo permeation, in vivo pharmacokinetic and pharmacodynamics study. RESULTS: The optimized AG bilosomes (AG-BILopt) has shown the vesicle size 183.25 ± 2.43 nm, entrapment efficiency 81.67 ± 4.87%. TEM image showed a spherical shape vesicle with sharp boundaries. The drug release study revealed a significant enhancement in AG release (79.45 ± 4.18%) from AG-BILopt as compared to free AG-dispersion (25.47 ± 3.64%). The permeation and pharmacokinetic studies result revealed 4.49 times higher flux and 4.67 folds higher AUC0-t than free AG-dispersion. The antidiabetic activity results showed significant (P < 0.05) enhancement in therapeutic efficacy than free AG-dispersion. The results also showed marked improvement in biochemical parameters. CONCLUSION: Our findings suggested, the prepared apigenin loaded bilosomes was found to be an efficient delivery in the therapeutic efficacy in diabetes.