The Current Status of Exenatide Once Weekly

Kulasa, Kristen

doi:10.4137/cmt.s3083

Cited by 5 publications

(1 citation statement)

References 42 publications

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“…Multiple drug delivery strategies were explored in the attempts to address this challenge. For example, chemical modification of proteins with poly(ethylene glycol) (PEG), known as PEGylation [3], or incorporation of proteins into poly(D,L-lactic-co-glycolide) (PLGA) particles [4, 5] increased stability and bioavailability of certain proteins and resulted in development of the Food and Drug Administration (FDA) approved products for various peripheral diseases. However, neither of these technologies has shown much promise so far in delivering protein therapeutics to the brain for treatment of CNS related diseases.…”

Section: Introductionmentioning

confidence: 99%

Agile delivery of protein therapeutics to CNS

Xiang

Manickam

Brynskikh

et al. 2014

Journal of Controlled Release

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A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics.

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Section: Introductionmentioning

confidence: 99%