Biocompatible disulphide cross-linked sodium alginate derivative nanoparticles for oral colon-targeted drug delivery

Abstract

The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colonspecific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteaminebased disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential¼ À58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 mg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery. ARTICLE HISTORY

Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment

“…Lim Vuanghao et al published a report on their use of biocompatible disulphide cross-linked sodium alginate derivative NPs, for targeted oral delivery of PTX to treat colon cancer. They formulated self-assembled cysteamine based disulphide cross-linked sodium alginate NPs, aimed at improving the delivery of PTX to the colon cancer cells [47]. The drug-loaded NPs were reported to have exhibited 77.1% EE and a cumulative drug release of 45.1% in pH 6 medium with GSH.…”

Strategies to Functionalize the Anionic Biopolymer Na-Alginate without Restricting Its Polyelectrolyte Properties

“…Oliver et al demonstrated that the conjugation of the antioxidant catechin to alg-aldehyde under acidic conditions led to up to 22% functionalization with catechin, involving both nucleophilic addition to the carbonyl group and post-esterification of the carboxylate functionality ( Figure 10) of the functionalized polymers, the chemical modification with thiol-containing units was the key to the sorption properties, which was probably due to their role as cross-linkers between the polymeric chains [88]. 3-11% NaBH4 Drug delivery [86] Imine formation on oxidized alg derivatives was also applied to engineer alg/chitosan or alg/hyaluronic acid hydrogels for protein delivery [90] and cardiac tissue engineering [91].…”

“…Oliver et al demonstrated that the conjugation of the antioxidant catechin to alg-aldehyde under acidic conditions led to up to 22% functionalization with catechin, involving both nucleophilic addition to the carbonyl group and post-esterification of the carboxylate functionality ( Figure 10) [92]. NaBH 4 Drug delivery [86] Numerous alg derivatives resulting from reductive amination were developed for drug delivery purposes. The conjugation of amino-thiophenol [85], cysteine [82], or cysteamine [86] to oxidized alg led to self-assembled nanospheres, cross-linked through disulfide bridge formation, which are sensitive to redox potential variations for controlled release of the entrapped drugs.…”

“…NaBH 4 Drug delivery [86] Numerous alg derivatives resulting from reductive amination were developed for drug delivery purposes. The conjugation of amino-thiophenol [85], cysteine [82], or cysteamine [86] to oxidized alg led to self-assembled nanospheres, cross-linked through disulfide bridge formation, which are sensitive to redox potential variations for controlled release of the entrapped drugs. Imine-functionalized alg-derived self-assembled nanoparticles were obtained by the conjugation of oxidized alg to doxorubicin and an additional encapsulation of curcumin for the co-delivery of both drugs to tumor cells, which was triggered by the pH variation in the tumoral environment [87].…”

Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery

“…In vitro drug release studies were conducted at 37 ± 0.1 • C in a shaker incubator at 50 rpm. Hydrochloric acid solution (pH 1.0, stomach), phosphate buffer solution (pH 7.4, small intestine), and phosphate buffer solution (pH 6.0) with and without GSH (colon) were used to simulate the pH and reducing environment of the GIT [20,44].…”