Role of nanostructured aggregation of chitosan derivatives on [5-methionine]enkephalin affinity

Affinities of quaternary ammonium-chitosan conjugates, their thiolated derivatives and corresponding nanostructured aggregates towards the hydrophilic drug [5-methionine]enkephalin were compared by Nuclear Magnetic Resonance (NMR) spectroscopic methods based on proton selective relaxation rate measurements. Nanoaggregates showed enhanced drug affinity in comparison with corresponding polymers, especially in the case of thiolated systems

Chitosan-Based Nanoparticles Containing Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress

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 water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

Preparation and in vitro evaluation of chitosan matrices for colonic controlled drug delivery

Purpose. The work was aimed at studying in vitro the release of 5-aminosalicylic acid (5-ASA) or diclofenac sodium (DS) from matrices based on chitosan (Ch) or Ch hydrochloride (Ch-HCl), destined to be introduced into enteric-coated capsules for controlled release to the colon. Methods. Matrices (diameter, 6 mm; weight, 50 mg) were prepared by compression of Ch or Ch-HCl microparticles mixed with 20% 5-ASA or DS powder. Drug release from matrices to isotonic neutral buffers of different molarity was studied in vitro. In some cases, matrix incubation in rat cecal contents preceded the release test. Results. The matrices, especially the Ch-HCl-based ones, swelled in the dissolution medium without disintegrating. Drug release was diffusion-controlled and followed square-root-time kinetics. Release depended on the pH-dependent aqueous solubility of the drug. The internal pH of the swollen Ch-HCl-based matrix was acidic, so 5-ASA solubility and release were influenced by penetration of salts from the external buffer. In the Ch-HCl-based matrix DS was converted into the scarcely soluble diclofenac free acid, which prolonged the time for release of 50% dose excessively (t(50)=11.26 h). The enzymatic action of rat cecal microflora accelerated drug release from the Ch-HCl-based matrix. On the other hand, neither such a microflora nor the external medium hydrodynamics significantly affected drug release from the Ch-based matrix. Conclusions. The Ch-based matrix was a reliable colonic controlled-release system for 5-ASA (t(50)=1.97 h) or DS (t(50)=3.58 h). For in vivo application, a number of matrices adequate to make up the therapeutic drug dose should be introduced into enteric-coated size 00 capsules

Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

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