Construction of Chitosan/Alginate Nano-Drug Delivery System for Improving Dextran Sodium Sulfate-Induced Colitis in Mice

Abstract

(1) Background: In the treatment of ulcerative colitis (UC), accurate delivery and release of anti-inflammatory drugs to the site of inflammation can reduce systemic side effects. (2) Methods: We took advantage of this goal to prepare resveratrol-loaded PLGA nanoparticles (RES-PCAC-NPs) by emulsification solvent volatilization. After layer-by-layer self-assembly technology, we deposited chitosan and alginate to form a three-layer polyelectrolyte film. (3) Results: It can transport nanoparticles through the gastric environment to target inflammation sites and slowly release drugs at a specific pH. The resulting RES-PCAC-NPs have an ideal average diameter (~255 nm), a narrow particle size distribution and a positively charged surface charge (~13.5 mV). The Fourier transform infrared spectroscopy showed that resveratrol was successfully encapsulated into PCAC nanoparticles, and the encapsulation efficiency reached 87.26%. In addition, fluorescence imaging showed that RES-PCAC-NPs with positive charges on the surface can effectively target and accumulate in the inflammation site while continuing to penetrate downward to promote mucosal healing. Importantly, oral RES-PCAC-NPs treatment in DSS-induced mice was superior to other results in significantly improved inflammatory markers of UC. (4) Conclusions: Our results strongly prove that RES-PCAC-NPs can target the inflamed colon for maximum efficacy, and this oral pharmaceutical formulation can represent a promising formulation in the treatment of UC.

Multiple Roles of Chitosan in Mucosal Drug Delivery: An Updated Review

“…A dual pH-/thermo-responsive hydrogel was designed based on a PEC of norbornene-functionalized CS and polyacrylic acid, which was synergized via “click chemistry” using a thermo-sensitive polymeric crosslinker (bistetrazine-poly(N-isopropyl acrylamide); the obtained hydrogel, loaded with a model drug, showed a limited drug release in gastric conditions and an almost complete release in colonic conditions (pH 7.4) [ 325 ]. The CS PECs formation was also exploited with several other polymers, such as pectin [ 326 ], alginate [ 327 , 328 , 329 ], thiolated dextran [ 330 ] and gellan gum [ 331 ], leading to the creation of beads or micro- or nanoparticles aimed for colon delivery.…”

Chitosan-based oral colon-specific delivery systems for polyphenols: recent advances and emerging trends

“…232 After depositing chitosan and alginate on the surface of PLGA nanoparticles, the loaded curcumin or resveratrol could smoothly reach the colon. 233,234 On the swelling mechanism of drug release, the gel coating of chitosan/alginate exhibits pH-dependent behavior. Interestingly, it has been reported that inflammation of the colonic mucosa is accompanied by depletion of the mucus layer and the in situ accumulation of positively charged proteins, including transferrin, 236 which has been applied to develop an inflammation-targeting carrier with a negative charge for preventing IBD 45,237 (Fig.…”

Oxidative Stress and Antioxidant Nanotherapeutic Approaches for Inflammatory Bowel Disease

“…The utility of polyphenol in nano-formulations aims to improve its solubility, activity, and stability, making the compound therapeutically more effective without adverse effects. Many nano-encapsulated polyphenols (curcumin, resveratrol, berberin, epigallocatechin gallate (EGCG), tannic acid, rosmarin acid, oleuropein, and ginsenoside) have recently been proved to have anti-inflammatory properties and have an important role in the management of IBD [ 10 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 67 ]. For the same reason, the polyphenol-rich extracts such as grape seed extract, green tea extract, and lycin barbarum extract have the potential to treat intrinsic inflammation as well [ 66 , 68 , 69 , 70 ].…”