Hydrogels for delivery of bioactive agents: A historical perspective

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Abstract

Since 1960 when the history of modern hydrogels began significant progress has been made in the field of controlled drug delivery. In particular, recent advances in the so-called smart hydrogels have made it possible to design highly sophisticated formulations, e.g., self-regulated drug delivery systems. Despite intensive efforts, clinical applications of smart hydrogels have been limited. Smart hydrogels need to be even smarter to execute functions necessary for achieving desired clinical functions. It is necessary to develop novel hydrogels that meet the requirements of the intended, specific applications, rather than finding applications of newly developed hydrogels. Furthermore, developing smarter hydrogels that can mimic natural systems is necessary, but the fundamental differences between natural and synthetic systems need to be understood. Such understanding will allow us to develop novel hydrogels with the new, multiple functions that we are looking for.

Section snippets

Research on hydrogels

The number of references published under the research topic of “hydrogel” has increased exponentially during the last decade. According to SciFinder®, the first reference on hydrogel appeared in 1894. Although the hydrogels described during that time period was a colloidal gel of inorganic salts, which are not exactly the same type of hydrogels we are dealing with nowadays, the use of the word “hydrogel” in as early as 1894 is very interesting. Since then, the term “hydrogel” was used to

Hydrogels for drug delivery

Analysis of the references on drug delivery by the index terms resulted in more than 1000 different terms. The most widely used index terms include pharmaceutical hydrogels, dissolution, physical swelling, and controlled release. Despite a large number of references related to hydrogel-based drug delivery systems, however, the actual number of hydrogel-based drug delivery systems or devices approved by the Food and Drug Administration (FDA) is extremely small. The clinically used hydrogel-based

Self-regulated drug delivery systems

One of the holy grails of controlled drug delivery is self-regulated insulin delivery systems. Insulin delivery is not like any other drug delivery where a sustained, long-term release can achieve an intended goal. Insulin release has to occur at the right time in the right amount. Insulin delivery starts with measuring the glucose concentration in the blood or in an environment in equilibrium with that of the blood. Once the glucose level increases, the right amount of insulin has to be

Current and future research on hydrogels

As mentioned above, the number of FDA-approved clinical products based on hydrogels is rather small. There may be many reasons for this, but one of them is that the current approach of hydrogel research for drug delivery is not quite in sync with formulation development. The current approach is to synthesize new smart hydrogels having new properties. Once a new hydrogel is synthesized, then suitable applications are sought out for the hydrogel. Since the new hydrogel was not prepared for any

Mimicking natural systems

One approach of designing a successful clinical formulation is to mimic natural systems. After all, a holy grail of making a self-regulated insulin delivery system is just to mimic the pancreas, a natural system. Mimicking natural systems, however, is not as easy as it sounds, because there are fundamental differences in the way that natural systems are formed and the way that synthetic systems are created, as shown in Fig. 4 [14]. In natural systems, evolution occurs to increase the efficacy,

Acknowledgments

This study was supported in part by NIH through grants CA129287 and GM095879, and Showalter Research Trust Fund.

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This review is part of the Advanced Drug Delivery Reviews theme issue on "25th Anniversary issue—Advanced Drug Delivery: Perspectives and Prospects".

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