Journal
DRUG DELIVERY
Volume 24, Issue 1, Pages 1513-1525Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2017.1381200
Keywords
Porous microspheres; layer-by-layer; glucose sensitive; sustained release; smart drug delivery system
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Funding
- Science and Technology Commission of Shanghai Municipality [16410723700]
- National Natural Science Foundation of China [81360128]
- Biomedical Textile Materials 111 Project of the Ministry of Education of China [B07024]
- UK-China Joint Laboratory for Therapeutic Textiles (based at Donghua University)
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Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N-vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83 +/- 0.15 and 82.6 +/- 5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.
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