Fucoidan-based hydrogels particles as versatile carriers for diabetes treatment strategies

Abstract

There is a current lack of fully efficient therapies for diabetes mellitus, a chronic disease where the metabolism of blood glucose is severely hindered by a deficit in insulin or cell resistance to this hormone. Therefore, it is crucial to develop new therapeutic strategies to treat this disease, including devices for the controlled delivery of insulin or encapsulation of insulin-producing cells. In this work, fucoidan (Fu) – a marine sulfated polysaccharide exhibiting relevant properties on reducing blood glucose and antioxidant and anti-inflammatory effects – was used for the development of versatile carriers envisaging diabetes advanced therapies. Fu was functionalized by methacrylation (MFu) using 8% and 12% (v/v) of methacrylic anhydride and further photocrosslinked using visible light in the presence of triethanolamine and eosin-y to produce hydrogel particles. Degree of methacrylation varied between 2.78 and 6.50, as determined by ¹HNMR, and the produced particles have an average diameter ranging from 0.63 to 1.3 mm (dry state). Insulin (5%) was added to MFu solution to produce drug-loaded particles and the release profile was assessed in phosphate buffer solution (PBS) and simulated intestinal fluid (SIF) for 24 h. Insulin was released in a sustained manner during the initial 8 h, reaching then a plateau, higher in PBS than in SIF, indicating that lower pH favors drug liberation. Moreover, the ability of MFu particles to serve as templates for the culture of human pancreatic cells was assessed using 1.1B4 cell line during up to 7 days. During the culture period studied, pancreatic beta cells were proliferating, with a global viability over 80% and tend to form pseudo-islets, thus suggesting that the proposed biomaterial could be a good candidate as versatile carrier for diabetes treatment as they sustain the release of insulin and support pancreatic beta cells viability.

Keywords:

• Fucoidan
• diabetes mellitus
• marine biomaterials
• photo-crosslinking
• insulin
• pancreatic cells

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We acknowledge ERDF for the financial support through POCTEP Project 0687_NOVOMAR_1_P, under the scope of INTERREG 2007-2013, and project 0302_CVMAR_I_1_P, under the scope of INTERREG España-Portugal 2014-2020, and Structured Projects NORTE-01-0145-FEDER-000021, NORTE-01-0145-FEDER-000023 and ATLANTIDA (ref. NORTE-01–0145-FEDER-000040), under the scope of Programa Operacional Regional do Norte (Norte 2020). Funding from the Portuguese Foundation for Science and Technology for doctoral grant (SFRH/BD/112139/2015) and post-doctoral grant (SFRH/BPD/85790/2012) is also acknowledged.