No abstract

Cherries are known for their nutraceutical properties, in particular for their antioxidant ability due to their polyphenol content, which causes a reduction of cardiovascular disease (CVD) risk factors. However, once ingested these molecules are degraded in the Gastrointestinal (GI) tract before reaching the blood, which is the action site. The object of the present work is to evaluate the ability of cherry extract (CE), encapsulated in nanoparticles (NPs) based on different chitosan (Ch) derivatives, to promote a protective effect of human umbilical vein endothelial cells (HUVECs) involved in vascular dysfunction against oxidative stress. CE-loaded NPs based on quaternary ammonium chitosan (NP1) and an S-protected thiolated derivative thereof (NP2) were prepared. The mean particle size (NP1 344.9 ± 17.8, NP2 339.9 ± 68.2 nm), the polydispersity index, the encapsulation efficiency (NP1 78.4 ± 4.5, NP2 79.8 ± 0.6%), and the zeta potential (NP1 14.8 ± 0.3, NP2 15.8 ± 0.5 mV) did not appear to be significantly different. Both NP types improved the CE apparent permeation parameters with respect to the control. Conversely, CE-loaded NP2 protected HUVECs from oxidative stress and reduced reactive oxygen species (ROS) production more than CE-loaded NP1 and free CE. In addition to promoting HUVEC resistance, NP2 could be a useful tool to overcome the problem of cherry seasonality.

A thermosensitive ophthalmic hydrogel (TSOH) – fluid at 4°C (instillation temperature), semisolid at 35°C (eye temperature), which coupled the dosing accuracy and administration ease of eyedrops with the increased ocular bioavailability of a hydrogel – was prepared by gelling a chitosan hydrochloride (ChHCl) solution (27.8 mg/mL) medicated with 1.25 mg/mL 5-fluorouracil (5-FU) with β-glycerophosphate 0.8 mg/mL. Polymer mixtures, where Ch was partially (10%, 15%, or 20%) replaced by quaternary ammonium–chitosan conjugates (QA-Ch) or thiolated derivatives thereof, were also used to modulate 5-FU-release properties of TSOH. Also, Ch-based nanoparticles (NPs; size after lyophilization and redispersion 341.5±15.2 nm, polydispersity 0.315±0.45, ζ-potential 10.21 mV) medicated with 1.25 mg/mL 5-FU prepared by ionotropic cross-linking of Ch with hyaluronan were introduced into TSOH. The 5-FU binding by TSOH polymers in the sol state was maximum with plain Ch (31.4%) and tended to decrease with increasing QA presence in polymer mixture. 5-FU release from TSOH with or without NPs was diffusion-controlled and linear in √t. The different TSOH polymers were compared on a diffusivity basis by comparing the slopes of √t plots. These showed a general decrease with NP-containing TSOH, which was the most marked with the TSOH, where Ch was 20% replaced by the derivative QA-Ch50. This formulation and that not containing NP were instilled in rabbits and the 5-FU transcorneal penetration was measured by analyzing the aqueous humor. Both TSOH solutions increased the area under the curve (0–8 hours) 3.5 times compared with the plain eyedrops, but maximum concentration for the NP-free TSOH was about 0.65 μg/mL, followed by a slow decline, while the NP-containing one showed a plateau (0.25–0.3 μg/mL) in a time interval of 0.5–7 hours. This is ascribed to the ability of this TSOH to control drug release to a zero order and that of NPs to be internalized by corneal cells

No abstract

Nanoparticles (NP) only different in mucoadhesivity are compared for impact on drug oral bioavailability. Two polymeric NP types based on quaternary ammonium-chitosan (NP QA-Ch) and S-protected thiolated derivative thereof (NP QA-Ch-S-pro), respectively, containing the macromolecular drug model, FD4, were prepared by crosslinking each polymer with reduced MW hyaluronic acid. The structure of basic polymers was determined by HNMR analysis. NP were similar in size (371 ± 38 vs. 376 ± 82 nm); polydispersity index (0.39 ± 0.08 vs. 0.41 ± 0.10); zeta potential (13.4 ± 0.9 vs. 11.9 ± 1.2 mV); reversible interactions with drug (bound drug, 67 vs. 66%); encapsulation efficiency (23 ± 5 vs. 23 ± 8%); release properties (15% released in 15 h in both cases); and apparent permeation across excised rat intestine (P, 8.8 ± 0.8 vs. 10 ± 1 cm/s). Then the differences in NP transport ratio through mucus (TR, 0.75 vs. 0.37) and adhesion to excised rat intestinal mucosa (adsorbed fraction, 23 ± 3 vs. 45 ± 2%) were ascribed to higher mucoadhesivity of NP QA-Ch-S-pro compared to NP QA-Ch. This directly influenced drug oral bioavailability in rats (T, 1 vs. 2 h; AUC, 1.7 ± 0.3 vs. 2.9 ± 0.4 μg/mL min, for NP QA-Ch and NP QA-Ch-S-pro, respectively). Mucoadhesivity increases drug bioavailability by retaining NP at its absorption site and opposing its transit down the GI tract. Data on drug accumulation in rat liver allows the assertion that NP is absorbed by transcytosis across intestinal epithelium and transported from blood into liver by Kuppfer cells.