Self-regulated delivery systems

Makino K, Mack EJ, Okano T, Kim SW. A microcapsule self-regulating delivery system for insulin. J Controlled Release 1990 12 235-239. 

Taylor Ml, Tanna S, Cockshott S, and Vaitha R. A self-regulated delivery system using unmodified solutes in glucose-sensitive gel membranes. Journal of Pharmacy and Pharmacology 1994 46 (Suppl. 2) 1051a. 

This polymer system has been extensively investigated in a number of applications which can be divided into (a) use in an insulin self-regulated delivery system, (b) in short term deliver) and in (c) long term deliver). ... 

R Alhaique, M Marchetti, FM Riccieri, E Santucci. A polymeric film responding in diffusion properties to environmental pH stimuli A model for a self-regulating drug delivery system. J Pharmacol 33 413-418, 1981. 

With the advance of pharmaceutical science, it has been recognized that constant release is not the only way to maximize drug effectiveness and minimize side effects and that the assumptions used for constant release rate sometimes fail due to physiological conditions. From this perspective, zero-order dmg release is not acceptable in all cases and externally modulated or self-regulating dmg delivery systems have been developed as novel approaches to deliver dmgs as required. To realize such dmg delivery systems, it is important to constmct a system where the dmg itself senses environmental stimuli and responds appropriately to control the dmg release. For this purpose, the phase transition polymers have been intensively exploited as a candidate material during last decade [21]. 

Use of Bioerodible Polymers in Self-Regulated Drug Delivery Systems... 

In biphasic reactors or two-phase partitioning bioreactors (TPPB), the substrate is located mostly in the immiscible phase and diffuses to the aqueous phase. The enzyme catalyzes conversion of the substrate at the interface and/or in the aqueous phase. The product/s of the reaction then may partition to the organic phase. The system is self-regulated, as the substrate delivery to the aqueous phase is only directed by the partitioning ratio between the two phases and the enzymatic reaction rate [53]. The use of ionic liquid/supercritical carbon dioxide for enzyme-catalyzed transformation is gaining attention [69]. 

Further development of the self-regulating insulin delivery system has utilized the complex of glycosylated insulin-concanavalin A, which is encapsulated inside a polymer membrane. As glucose penetrates into the system, it activates the release of glycosylated insulin from the complex for a controlled release from the system (Fig. 28). The amount of insulin released is thus self-regulated by the concentration of glucose that has penetrated into the insulin delivery system. 

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