TY - JOUR T1 - Inflammation-specific targeted carriers for local drug delivery to inflammatory bowel disease. JF - Biomaterials Y1 - 2022 A1 - Kotla, Niranjan G A1 - Singh, Rajbir A1 - Baby, Becca V A1 - Rasala, Swetha A1 - Rasool, Jawad A1 - Hynes, Sean O A1 - Martin, Darrell A1 - Egan, Laurence J A1 - Vemula, Praveen K A1 - Jala, Venkatakrishna R A1 - Rochev, Yury A1 - Pandit, Abhay AB -

Delivering drugs directly to the inflamed intestinal sites to treat inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis, is highly challenging. Recent advances in colitis therapy medications are expanding opportunities for improving local on-site drug availability by minimising the associated systemic side-effects. Drug delivery with targeted carrier systems has shown the potential to increase site-specificity, stability, and therapeutic efficacy. Herein, we report the development of a strong anionic charged inflammation targeted nanocarriers (IT-NCs) loaded with an immunosuppressant model drug. This system showed preferential adhesion on a charge-modified surface in vitro, and in both dextran sulfate sodium (DSS) and TNBS colitis mice in vivo models. IT-NCs showed improved colitis phenotype therapeutic efficacy in both animal models compared to free drug. Furthermore, ex vivo study of colon tissue biopsies from patients with colitis revealed that IT-NCs adhered preferentially to inflamed biopsies compared to normal. Together, our results suggest that IT-NCs have promising therapeutic potential as delivery carriers' in colitis management.

VL - 281 ER - TY - JOUR T1 - Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives. JF - Adv Drug Deliv Rev Y1 - 2018 A1 - Kotla, Niranjan G A1 - Rana, Shubhasmin A1 - Sivaraman, Gandhi A1 - Sunnapu, Omprakash A1 - Vemula, Praveen K A1 - Pandit, Abhay A1 - Rochev, Yury AB -

Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches. Amongst the different approaches reported, the use of biodegradable polysaccharide coated systems holds great promise in delivering drugs to the ulcerative regions. The present review focuses on major physiological gastro-intestinal tract challenges involved in altering the pharmacokinetics of delivery systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos and focusing on conventional to advanced disease responsive delivery strategies, highlighting their limitations and future perspectives in intestinal inflammation therapy.

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