Polymer Nanoparticles with 2-HP-ß-Cyclodextrin for Enhanced Retention of Uptake into HCE-T Cells.

Triamcinolone acetonide (TA), a medium-potency synthetic glucocorticoid, is primarily employed to treat posterior ocular diseases using vitreous injection. This study aimed to design novel ocular nanoformulation drug delivery systems using PLGA carriers to overcome the ocular drug delivery barrier and facilitate effective delivery into the ocular tissues after topical administration. The surface of the PLGA nanodelivery system was made hydrophilic (2-HP-ß-CD) through an emulsified solvent volatilization method, followed by system characterization. The mechanism of cellular uptake across the corneal epithelial cell barrier used rhodamine B (Rh-B) to prepare fluorescent probes for delivery systems. The triamcinolone acetonide (TA)-loaded nanodelivery system was validated by in vitro release behavior, isolated corneal permeability, and in vivo atrial hydrodynamics. The results indicated that the fluorescent probes, viz., the Rh-B-(2-HP-ß-CD)/PLGA NPs and the drug-loaded TA-(2-HP-ß-CD)/PLGA NPs, were within 200 nm in size. Moreover, the system was homogeneous and stable. The in vitro transport mechanism across the epithelial barrier showed that the uptake of nanoparticles was time-dependent and that NPs were actively transported across the epithelial barrier. The in vitro release behavior of the TA-loaded nanodelivery systems revealed that (2-HP-ß-CD)/PLGA nanoparticles could prolong the drug release time to up to three times longer than the suspensions. The isolated corneal permeability demonstrated that TA-(2-HP-ß-CD)/PLGA NPs could extend the precorneal retention time and boost corneal permeability. Thus, they increased the cumulative release per unit area 7.99-fold at 8 h compared to the suspension. The pharmacokinetics within the aqueous humor showed that (2-HP-ß-CD)/PLGA nanoparticles could elevate the bioavailability of the drug, and its Cmax was 51.91 times higher than that of the triamcinolone acetonide aqueous solution. Therefore, (2-HP-ß-CD)/PLGA NPs can potentially elevate transmembrane uptake, promote corneal permeability, and improve the bioavailability of drugs inside the aqueous humor. This study provides a foundation for future research on transocular barrier nanoformulations for non-invasive drug delivery.

The delivery of nanoparticles improves the pharmacokinetic properties of celecoxib to open a therapeutic window for oral administration of insoluble drugs.

A sensitive and reliable LC-MS/MS method is established and validated to determine the concentration of celecoxib, in the serum of cynomolgus monkey, using celecoxib-D7 as an internal standard. The pharmacokinetic process was investigated after giving Celebrex, celecoxib nanoparticles (CXB-NPs) and hyaluronic acid celecoxib nanoparticles (HA-CXB-NPs) by intragastric (i.g.) administration. Chromatographic separation was performed with a C18 column (2.1 × 100 mm, 2.6 µm) at 40°C with a mobile phase of 2‰ HCOOH in water and acetonitrile. The mass spectral acquisition was then performed in the multiple reaction monitoring mode, with negative ESI ion at m/z 380.0 → 316.0 and m/z 387.1 → 323.1 for celecoxib and celecoxib-D7, respectively. Good linearity was observed over the concentration range from 3 to 2,000 ng/ml (R2 = 0.9954). The intra- and inter-day precision and accuracy, matrix effect and extraction recovery, as well as stability, all met the determination requirements of biological samples. The pharmacokinetic parameters of Celebrex, CXB-NPs and HA-CXB-NPs were determined as: area under the curve, 1,855.98 ± 346.59, 1,908.00 ± 1,130.24 and 2,164.48 ± 657.47 h·ng/ml; peak concentration, 261.08 ± 113.26, 261.12 ± 94.67 and 263.34 ± 151.78 µg/L; time to peak concentration, 2.00 ± 1.22, 4.00 ± 0.00 and 3.60 ± 0.89 h; half-life, 4.39 ± 1.26, 2.33 ± 0.94 and 4.92 ± 3.13 h; relative bioavailability, 102.80 ± 49.62 and 116.63 ± 25.55%. The validated method was successfully applied to the pharmacokinetic study of celecoxib in cynomolgus monkey, after i.g. administration. The preparation of the nanoparticles of celecoxib and the modification of hyaluronic acid on the surface of nanoparticles could improve the bioavailability and prolong the circulation of celecoxib in vivo, which could lay the foundation for further development of celecoxib nanoparticles.