Synthesis of pH-Responsive Chitosan Nanocapsules for the Controlled Delivery of Doxorubicin

Abstract

Well-defined chitosan nanocapsules (CSNCs) with tunable sizes were synthesized through the interfacial cross-linking of N-maleoyl-functionalized chitosan (MCS) in miniemulsions, and their application in the delivery of doxorubicin (Dox) was investigated. MCS was prepared by the amidation reaction of CS with maleic anhydride in water/DMSO at 65 °C for 20 h. Subsequently, thiol-ene cross-linking was conducted in oil-in-water miniemulsions at room temperature under UV irradiation for 1 h, using MCS as both a surfactant and precursor polymer, 1,4-butanediol bis(3-mercapto-propionate) as a cross-linker, and D-α-tocopheryl poly(ethylene glycol) 1000 succinate as a cosurfactant. With the increase in cosurfactant concentration in the reaction systems, the sizes of the resulting CSNCs decreased steadily. Dox-loaded CSNCs were readily prepared by in situ encapsulation of Dox during miniemulsion cross-linking. With acid-labile β-thiopropionate cross-linkages, the Dox-loaded CSNCs demonstrated a faster release rate under acidic conditions. Relative to free Dox, Dox-loaded CSNCs exhibited enhanced cytotoxicity toward MCF-7 breast cancer cells without any noticeable cytotoxicity from empty CSNCs. The effective delivery of Dox to MCF-7 breast cancer cells via Dox-loaded CSNCs was also observed.

Functional Colloidal Stabilization

“…Styrene-functionalized PDMA (Table 3, entry 8) was employed as a surfmer in the emulsion polymerization of poly(2-vinylpyridine) (P2VP) and DVB as a crosslinker to obtain pH responsive polymer dispersions. [110] 3.2.2.2. These colloids were also used as Pickering emulsifiers to stabilize water-in-undecanol emulsions.…”

“…[22,129] Such stabilizers are mostly biocompatible or bioactive and may be useful in drug delivery systems. [110] Laroui et al prepared hyaluronic acid (HA) and chondroitin sulfate (CS) functionalized NPs (700 nm) by double emulsion/solvent evaporation for controlled drug delivery to cartilage cells ( Table 8, entry 1). [110] Laroui et al prepared hyaluronic acid (HA) and chondroitin sulfate (CS) functionalized NPs (700 nm) by double emulsion/solvent evaporation for controlled drug delivery to cartilage cells ( Table 8, entry 1).…”

Manufacturing Process and Property Evaluations of Polyethylene Oxide/Water-Soluble Chitosan Electrospun Nanofiber Membranes

“…Electrospinning is a relatively simple and efficient method, and it has advantages of ease of use, high surface area, the , Wen-Cheng Chen 6 and Ching-Wen Lou 7,a* 1 ultrafine diameter, and high degree of porosity [1,2]. These advantages enable the nanofiber membranes to facilitate the reorganization of skin tissues, and help the removal of secretion as well as the preservation of moisture.…”

“…Chitosan is only dissolved in acid, which raises concerns about possible damage to cells in biomedicine. Thus, using water-soluble chitosan may exclude the toxicity caused by acid solution and damage to biological cells clinically [5,6].…”

Controlling Properties and Cytotoxicity of Chitosan Nanocapsules by Chemical Grafting

“…Active research is now focused on the use of hydrophilic biopolymers as carrier coatings because of their biocompatibility and biodegradability [19,20]. Chitosan (CS) has been used for the development of sustained release carriers, mucoadhesive formulations, and peptide drug absorption systems [21,22,23,24]. It is currently employed to prepare nanomaterials with mucoadhesive properties since its positive charges allow the interaction of particles with the negative charge of mucin, resulting in a better interaction with mucosal tissues and with epithelial cells.…”