Gadziński Piotr, Skotnicka Agnieszka, Lisiak Natalia, Totoń Ewa, Rubiś Błażej, Florek Ewa, Mlynarczyk Dariusz T, Szybowicz Mirosław, Nowak Ewelina, Osmałek Tomasz
Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznań, Poland.
Doctoral School, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Poznań, Poland.
Pharmaceutics. 2025 Apr 25;17(5):569. doi: 10.3390/pharmaceutics17050569.
Many orally administered drugs are either unstable in the acidic environment of the stomach or cause moderate to severe side effects in the upper gastrointestinal tract (GIT). These limitations can reduce therapeutic efficacy, discourage patient compliance, worsen the disease, and even contribute to the risk of cancer development. To overcome these issues, drug release often needs to be modified and targeted to the distal parts of the GIT. This is typically achieved through the use of pH-sensitive polymer coatings or incorporation into polymeric delivery systems. With this in mind, the aim of this project was to design, develop, and characterize gellan gum-based beads for colon-specific prolonged release of mesalazine, with potential application in the chemoprevention and treatment of bowel diseases. The dehydrated capsules were characterized using Raman spectroscopy and scanning electron microscopy. The crosslinked gellan gum was additionally evaluated for cytotoxicity. Key parameters such as pH-dependent swelling behavior, drug content, encapsulation efficiency, and drug release in simulated gastrointestinal fluids were also assessed. Furthermore, the behavior of the capsules in the gastrointestinal tract was studied in a rat model to evaluate their in vivo performance. Significant differences in drug release profiles were observed between formulations crosslinked solely with calcium ions and those additionally crosslinked with glutaraldehyde (GA). The incorporation of GA effectively prolonged the release of mesalazine. These findings were further supported by in vivo studies conducted on Wistar rats, where the GA-crosslinked formulation demonstrated a markedly extended release compared to the formulation prepared using only ionotropic gelation. The combination of ionotropic gelation and glutaraldehyde crosslinking in gellan gum-based beads appears to be a promising strategy for achieving colon-specific prolonged release of mesalazine, facilitating targeted delivery to the distal regions of the gastrointestinal tract.
许多口服药物在胃的酸性环境中不稳定，或者在上消化道（GIT）中会引起中度至重度的副作用。这些局限性会降低治疗效果，降低患者的依从性，使病情恶化，甚至增加癌症发生的风险。为了克服这些问题，药物释放通常需要进行调整，并靶向于胃肠道的远端部位。这通常通过使用pH敏感的聚合物包衣或将药物掺入聚合物递送系统来实现。考虑到这一点，本项目的目的是设计、开发和表征基于结冷胶的微珠，用于美沙拉嗪的结肠特异性长效释放，潜在应用于肠道疾病的化学预防和治疗。使用拉曼光谱和扫描电子显微镜对脱水胶囊进行表征。此外，还对交联结冷胶的细胞毒性进行了评估。还评估了关键参数，如pH依赖性溶胀行为、药物含量、包封效率以及在模拟胃肠液中的药物释放。此外，在大鼠模型中研究了胶囊在胃肠道中的行为，以评估其体内性能。仅用钙离子交联的制剂与另外用戊二醛（GA）交联的制剂之间，在药物释放曲线方面观察到了显著差异。GA的加入有效地延长了美沙拉嗪的释放。在Wistar大鼠上进行的体内研究进一步支持了这些发现，与仅使用离子凝胶法制备的制剂相比，GA交联制剂显示出明显延长的释放。基于结冷胶的微珠中离子凝胶法和戊二醛交联的结合似乎是实现美沙拉嗪结肠特异性长效释放、促进靶向递送至胃肠道远端区域的一种有前景的策略。
