Design and Investigation of Alginate Coated Solid Lipid Nanoparticles for Oral Insulin Delivery

Abstract

Introduction:The conventional subcutaneous administration of insulin has been associated with several limitations leading to poor patient compliance. The poor oral bioavailability of insulin due to degradation by gastrointestinal enzymes and secretions can be countered by the use of protective carriers such as solid lipid nanoparticles that are capable of being taken up by the Peyer's patches. The aim of the investigation was to design and investigate alginate coated solid lipid nanoparticles (SLN) of insulin for oral administration. Materials and Methods: The SLN were prepared from glyceryl behenate and glyceryl monostearate and coated with mucoadhesive polymer, sodium alginate. The SLN were evaluated for size, shape, zeta potential, drug content, in vitro release and ex vivo drug permeation through goat intestinal mucosa and Caco-2 cell monolayer model. Results and Discussion: Transmission electron microscopy revealed spherical particles of uniform size distribution. In vitro drug release using the reverse dialysis method revealed that the alginate coating maintained the potency of insulin in simulated GI fluids and also provided sustained release. Absorption enhancement was demonstrated in ex vivo permeation studies in the goat intestinal mucosal model as well as in the Caco-2 cell monolayer model. The oral administration of alginate-coated insulin SLN in streptozotocin induced diabetic rats resulted in a significant hypoglycemic effect as compared to that of uncoated insulin-loaded SLN. The percentage glycemia at the end of 10 h was statistically significant (p<0.05) to oral insulin and the hypoglycemic levels reached were comparable to that of the conventional subcutaneous insulin. Conclusion: Alginate coated SLN has the potential of improving the absorption of insulin through intestinal mucosa and possibly its bioavailability.

Muco-Adhesive and Muco-Penetrative Formulations for the Oral Delivery of Insulin

“…To enhance the encapsulation efficiency of the carrier, solid lipid nanoparticles (SLN) were used. SLN particles with alginate coating showed sustained release, insulin permeation through the transcellular pathway, and significant hypoglycemic effect in diabetic rat models …”

“…SLN particles with alginate coating showed sustained release, insulin permeation through the transcellular pathway, and significant hypoglycemic effect in diabetic rat models. 35 In another study, self-nanoemulsifying drug delivery systems (SNEDDS) were developed by using a combination of surfactants. The MA properties were imparted through the coating of alginate and guar gum.…”

“…SLN particles with alginate coating showed sustained release, insulin permeation through the transcellular pathway, and significant hypoglycemic effect in diabetic rat models. 35 …”

Sodium Alginate—Natural Microencapsulation Material of Polymeric Microparticles

“…Microparticles made up of mucoadhesive polymers can improve the permeability of encapsulated medicinal substances of a protein nature (insulin) through the intestinal mucosa [ 125 ]. Thus, alginate microspheres can be used as pharmaceutical systems for oral insulin administration [ 126 ] because alginate slowly degrades in the body, protects the active substance from enzymatic degradation, improves its penetration through the intestinal wall [ 113 ] and facilitates the systemic absorption of insulin.…”

Recent Advances in Oral Insulin Therapy by Nanoparticulate Drug Delivery Systems: Systematic Review

“…Keçi bağırsak mukozasında yapılan ex vivo çalışmalarda kaplı KLN'ler, kaplı olmayan KLN'lere ve insülin çözeltisine göre daha üstün insülin geçirgenliği sağlamıştır ve bu durum sodyum aljinatın mukoadezif özellikleri ile açıklanmıştır. 67 silika Nanopartikülleri Silika nanopartikülleri, büyük gözenek hacmi ve gözenek boyutları sayesinde insülin gibi yüksek molekül ağırlığına ve büyüklüğe sahip protein ve polipeptid yapılı moleküllerin yüklenmesine olanak sağlaması, gözenek duvarları ve nanopartiküllerin geniş yüzeylerindeki silanol grupları ile işlevsel özelliklerinin düzenlenebilmesi, dayanıklı yapıları ile Gİ sistemin zorlu koşullarına karşı yüklenen molekülleri koruması, biyouyumlu olması, değiştirilmiş salım sağlaması ve düşük toksisiteli olması nedeniyle oldukça üstün görülen bir ilaç taşıyıcı sistemdir. 19 Juère ve ark., dendritik mezo gözenekli silika nanopartiküllerinin; küçük partikül boyutu, gözenekli yapısı ve negatif yüklü yüzeyleri ile yüksek miktarda insülin yüklenmesine olanak verirken bağırsak zarından insülin geçişine de izin verdiklerini bildirmişlerdir.…”