近年来,经粘膜药物递送系统(TDDS)已被广泛研究,因为它们保护治疗剂免于降解;改善药物在粘膜的停留时间;并促进药物长时间的持续释放。壳聚糖是一种经过充分研究的聚合物赋形剂,由于其生物相容性,无毒性,生物降解性,粘膜粘着剂,抗菌,低免疫原性。其在生理环境中有限的粘膜粘附性需要其化学修饰。这篇综述强调了用各种化学基团对壳聚糖进行化学修饰以生成各种功能化壳聚糖衍生物的最新进展,如硫醇化,丙烯酸酯,甲基丙烯酸酯化,硼酸,儿茶酚,和马来酰亚胺官能化的壳聚糖与母体壳聚糖相比具有优异的粘膜粘附能力。此外,它提供了不同的制备剂型,比如药片,水凝胶,电影,微米/纳米颗粒,和脂质体/脂质体,用于在各种粘膜途径(包括口服)内给药,颊,鼻部,眼,结肠,膀胱内,和阴道路径。来自这些药物制剂的临床前研究的报道数据已经揭示了治疗剂的受控和靶特异性递送,因为它们与粘膜表面上的硫醇基团形成共价键。所有的功能化壳聚糖衍生物表现出在粘膜表面长的药物停留时间和持续的药物释放具有优异的细胞通透性,药物疗效,和生物相容性。这些有希望的数据可以通过一致和密集的研究工作从研究实验室转化到诊所。
Recently, transmucosal drug delivery systems (TDDSs) have been extensively studied because they protect therapeutic agents from degradation; improve drug residence time at the mucosal membranes; and facilitate sustained drug release for a prolonged period. Chitosan is a well-researched polymeric excipient due to its biocompatibility, non-toxicity, biodegradability, mucoadhesive, antimicrobial, and low immunogenicity. Its limited mucoadhesiveness in the physiological environment necessitated its chemical modification. This review highlights the recent advances in the chemical modification of chitosan with various chemical groups to generate various functionalized chitosan derivatives, such as thiolated, acrylated, methacrylated, boronated, catechol, and maleimide-functionalized chitosans with superior mucoadhesive capabilities compared to the parent chitosan. Moreover, it presents the different prepared dosage forms, such as tablets, hydrogels, films, micro/nanoparticles, and liposomes/niosomes for drug administration within various mucosal routes including oral, buccal, nasal, ocular, colonic, intravesical, and vaginal routes. The reported data from preclinical studies of these pharmaceutical formulations have revealed the controlled and target-specific delivery of therapeutics because of their formation of covalent bonds with thiol groups on the mucosal surface. All functionalized chitosan derivatives exhibited long drug residence time on mucosal surfaces and sustainable drug release with excellent cellular permeability, drug efficacy, and biocompatibility. These promising data could be translated from the research laboratories to the clinics with consistent and intensive research effort.