幾丁聚醣奈米複合材料之局部與系統性感染治療應用潛力

Abstract

近來由於抗藥性細菌以及因感染造成的慢性傷口照護衍生費用的日漸增加，對現代醫療系統構成重大挑戰。以上問題通常需要具備局部釋放與持續療效的治療策略，以降低全身毒性並提升病患的用藥依從性。以上的醫療困境亟待解決，因此採用生物高分子所開發的奈米技術受到廣泛關注，藥物的定位釋放與組織再生方面更能展現解決現有問題的潛力。其中，幾丁聚醣作為一種天然、可生物降解且具良好黏附性的高分子材料便成發展奈米複合系統的多功能平台。 本研究強調幾丁聚醣奈米複合材料於兩種不同但互補的生物醫學應用中的潛力，突顯其作為一種具備生物相容性、可降解性與黏膜附著性的材料之多樣性。首先，研究合成了銀奈米粒子包覆於幾丁聚醣基質中的AgNPs-CHI，並進一步與β-1,3-葡聚醣及玻尿酸複合，製成AgNPs-CHI-Glu-HA，用作多功能傷口敷料。銀離子結合了幾丁聚醣所形成的生物複合材料展現出優異的生物相容性、血液相容性與促進凝血的特性，並可促進成纖維細胞遷移與傷口癒合，是有效組織再生的重要指標。儘管β-1,3-葡聚醣與HA的加入略微降低銀離子的擴散與抗菌效能，但其增強的安全性與組織修復效果使此權衡具有實際價值。 其次，為對抗具高度抗藥性的幽門螺旋桿菌(Helicobacter pylori)引起的腸胃道感染，本研究設計了包覆阿莫西林的幾丁聚醣–海藻酸鹽奈米粒 (CAANs)。此系統充分利用幾丁聚醣與海藻酸鹽的黏附特性，使奈米粒可停留於胃部黏膜表面並穿透黏液屏障，在胃酸環境中進行局部、持續性釋藥，有效避免游離態阿莫西林的酸性降解。體外試驗證實CAANs保留其抗菌活性，而體內實驗亦顯示其可延長胃部停留時間並顯著提高H. pylori 的根除率。 整體而言，這兩種策略展現出幾丁聚醣基材料可依照治療需求進行個體化設計，無論是作為金屬抗菌劑穩定劑以應用於傷口護理，抑或是保護並傳遞抗生素至胃腸道特定部位，其理化特性與生物功能的結合，使其成為次世代生物醫材的理想應用平台。在臨床應用上此一複合材料了我管對應於治療抗藥性細菌或是慢性傷口加速復原，皆展現高度應用潛力，並能有效降低系統性副作用。

Recently, the growing prevalence of antibiotic-resistant infections and the healthcare burden of chronic wounds have posed significant challenges to modern medical systems. These conditions often require localized and sustained therapeutic strategies that minimize systemic toxicity while improving patient compliance. In response, biopolymer-based nanotechnologies have attracted increasing attention for their potential to achieve targeted drug delivery and promote tissue regeneration. Among these materials, chitosan—a natural, biodegradable, and mucoadhesive polymer—has emerged as a versatile candidate for developing nanocomposite systems. This study highlights two distinct yet complementary biomedical applications of chitosan-based nanocomposites, emphasizing its versatility as a biocompatible, degradable, and adhesive biomaterial. First, silver nanoparticles were synthesized within a chitosan matrix (AgNPs-CHI) and further integrated with β-1,3-glucan and HA to form AgNPs-CHI-Glu-HA, a multifunctional wound dressing. This composite demonstrated excellent biocompatibility, hemocompatibility, and hemostatic properties. It also promoted fibroblast migration and accelerated wound healing—key indicators of effective tissue regeneration. Although the incorporation of β-1,3-glucan and HA slightly limited the diffusion of silver ions and thus reduced peak antibacterial efficiency, the trade-off was compensated by enhanced biosafety and regenerative performance. Second, to combat gastrointestinal infections caused by highly antibiotic-resistant Helicobacter pylori, chitosan–alginate-based nanoparticles (CAANs) were developed to encapsulate amoxicillin. These nanoparticles leveraged the mucoadhesive properties of both alginate and chitosan to adhere to the gastric mucosal surface and diffuse through the mucus barrier. This targeted localization enabled sustained drug release in the harsh acidic gastric environment, where free-form amoxicillin would typically degrade. In vitro assays confirmed that the CAANs preserved their antimicrobial activity, while in vivo studies demonstrated extended gastric residence time and improved H. pylori eradication efficiency. In summary, these two approaches demonstrate how chitosan-based systems can be tailored to meet different therapeutic objectives—either by stabilizing metallic antimicrobials for wound treatment or by protecting and delivering antibiotics within the gastrointestinal tract. The integration of chitosan’s physicochemical versatility and biological functionality underscores its potential as a next-generation platform for biomedical applications, offering significant clinical promise in infection control and tissue repair with minimal systemic side effects.