The effect of coencapsulation of bovine insulin with cyclodextrins in ethylcellulose microcapsules

Abstract

Polymeric microcapsules have been widely investigated for protein delivery. Common problems include: low stability, low encapsulation efficiency, lack of uniformity, and burst release. Cyclodextrins (CDs) are known to enhance stability and solubility of proteins in solution. This research examines the effect of alpha-, beta-, and gamma-CDs on: (1) stability, (2) encapsulation, and (3) release of insulin from ethylcellulose microcapsules. All CDs improved thermal stability of insulin by lowering the enthalpy of unfolding by 16-52%. alpha- and gamma-CDs also increased the encapsulation efficiency of insulin and improved uniformity of the microcapsule formulations. Two mathematical models were proposed to account for insulin release and consisted of multiple zero order and first order input processes, and a single first order output process. All CDs decreased the initial burst release of insulin by up to 30%. This research demonstrates the potential for CDs to improve stability, uniformity, and encapsulation of proteins in microcapsule formulations.

Formulation and <i>in vitro</i> evaluation of ibuprofen-loaded poly(D,L-lactide-co-glycolide) microparticles

“…If the PI is above 0.5, the PI loses its significance as an accurate measure of the width of the size of distribution, but can still be useful for comparative purposes. Low PI (less than 1) of any preparation is an indication of a better control of particle size [15]. The high negative values of the zeta potential obtained were due to uncapped end carboxyl groups.…”

“…However, initial burst release was observed for ibuprofen-loaded microparticles in the first hour, which was probably due to the rapid dissolution of the drug adhered onto the surface of the microparticles. Though, burst release may not be completely discouraged especially in conditions such as arthritis, as the initial amount of drug released can serve as a loading dose, while the subsequent release may serve as maintenance dose [8,15]. Figure 2 showed the drug content from the microparticles formulation after exposure to different storage conditions.…”

Cyclodextrin-Based Microcapsule Materials - Their Preparation and Physiochemical Properties

“…Different encapsulation methods result in products with variable morphology. For example, interfacial polymerization [44][45][46] and coacervation [8] methods generally produce well-defined microcapsule materials. In contrast, solvent evaporation may result in a microsphere [47][48][49] or microcapsule [50] materials, depending on the formulation conditions, e.g., the relative polarity of the solvent system, and the hydrophile-lipophile character of the microcapsule precursor materials [2,5].…”

“…In the case of encapsulation of bovine insulin with CD-containing ethylcellulose microcapsules [8], the core material (CD and bovine insulin complex) was dispersed in a dichloromethane solution of the coating material (ethylcellulose) with stirring. Phase separation and PAA/ -CD Emulsion-solvent N/A PNP Enhanced sorption ability [49] coacervation were induced by drop-wise addition of an immiscible solvent (n-hexane) to the solution.…”

“…Scheme 2) [6,7]. Guest molecules with variable size may favor complex formation with different CDs according to the host/guest size-fit relationship [8,9]. -CD is among the most widely studied because of its favourable cavity dimensions and complex formation stability with a wide range of small to medium sized guest molecules [10].…”