Gellan gum microparticles coated with resistant starch/pectin films as a strategy for oral administration of insulin

Author(s)

Andreia Bagliotti Meneguin

• Document type: Doctoral Thesis
• Press: Araraquara. 2016-03-15.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2016-01-14
• Advisor: Beatriz Stringhetti Ferreira Cury

Abstract

The development of a system that enables the oral administration of insulin (INS) is a major challenge, since the INS can be degraded in the upper portions of gastrintestinal tract (GIT). Its encapsulation within polymer matrices based on gellan gum (GG) should offer significant protection against the adverse conditions of the GIT, in addition to establishing mucoadhesive interactions. The coating of solid dosage forms with type 3 resistant starch is a rational strategy to achieve the colon specific drug delivery. Pectin also adds important properties in this sense, since it is resistant to proteases and amylases. The aim of this work was to obtain and to characterize GG MP (1.5, 2.0 or 2.5%), crosslinked with Al3+ (3 or 5%) and coated with films resistant starch/pectin for the oral administration of INS. The method employed was effective with a maximum yield of 99.10%, besides having allowed the obtaining of MP with a high encapsulation efficiency (up to 89.11%). The MP showed a mean diameter from 1012 to 1197 μm and circularity ranging from 0.68 to 0.81. The scanning electron microscopy indicated that the increase of the concentration of GG is responsible for obtaining more spherical MP and that INS is responsible for changing the rearrangement structures. The cross section showed a continuous and intact coating. According to the data of X-ray diffractograms, the MP have semi-crystalline structures. The liquid uptake was lower in acid media (218-615%) than in phosphate buffer pH 7.4 (432-812%) and 6.8 (373-703%) and the Korsmeyer-Peppas model was the best fitting for the liquid penetration mechanism in the samples, indicating that this occurred by Fickian diffusion (case-I). Enzymatic degradation tests showed that the system is able to protect the INS against degradation by up to approximately 80% after 120 min of incubation with trypsin and α-chymotrypsin. The in vitro release studies of INS were performed in apparatus I and IV, and the results showed that the coating developed offered a greater control of INS release, with reduced release rates in acidic medium, besides prolonging the release in the other media studied. Release profiles derived from the test apparatus I and IV fitted better to the kinetic model Weibull and Korsmeyer-Peppas and Higuchi and Korsmeyer-Peppas, respectively. Ex vivo bioadhesion test indicated that the samples obtained with 2.0 and 2.5% GG generate higher mucoadhesive forces (FMA). The ex vivo INS permeation was analyzed by the techniques of inverted and non-inverted intestine, and the latter revealed the importance of the coating to the increase of INS permeability. MP showed to modulate the opening of tight junctions, contributing for the INS permeation in both Caco-2 cells and in excised rat intestinal tissues. All MP induced a significant hypoglycemic effect with a maximum reduction in blood glucose of 51%. The effect was kept for up to 7h. The set of results suggests the use of the GG MP coated with resistant starch/pectin as INS carrier to enhance its permeability through the intestinal epithelium and its bioavailability after oral administration. (AU)

• FAPESP's process: 12/11798-0 - Gellan gum microcapsules coated with resistant starch/pectin as a strategy for oral administration of insulin.
• Grantee: Andréia Bagliotti Meneguin
• Support Opportunities: Scholarships in Brazil - Doctorate