Oligoarginine-linked polymers as a new class of penetration enhancers.
Summary of "Oligoarginine-linked polymers as a new class of penetration enhancers."
Oligoarginines, which are known as cell-penetrating peptides, enhance the cellular uptake of poorly membrane-permeable bioactive molecules that are chemically conjugated to them. We designed a novel polymer: oligoarginine-linked poly(N-vinylacetamide-co-acrylic acid), with the expectation that the polymers will enhance the cellular uptake of the bioactive molecules that are physically mixed with them. Oligoarginines were grafted onto the polymer backbone through the chemical reaction with acrylic acid functional groups. The changes in the blood glucose concentration after nasal administration of insulin with and without the polymer were monitored in mice. The blood glucose concentration was slightly reduced when insulin was given solely at a dose of 10IU/kg. A D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) with a grafting degree of 2% significantly enhanced the insulin-induced hypoglycemic effect. A similar enhancement was not observed when the polymer was substituted with intact D-octaarginine. The penetration-enhancing function of D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) increased dramatically with an increase in the grafting degree of D-octaarginine. Substitution of D-octaarginine with the corresponding optical isomer and an increase in the number of arginine residues rather reduced the penetration-enhancing function. In vitro cell studies also indicated that a D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) with a grafting degree of 17% enabled fluorescein isothiocyanate-dextran to effectively penetrate the cell membrane. Results demonstrated that our oligoarginine-linked polymer has a potential to provide a new class of penetration enhancers.
Affiliation
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Journal Details
This article was published in the following journal.
Name: Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20800631
- DOI: http://dx.doi.org/10.1016/j.jconrel.2010.08.022
Medical and Biotech [MESH] Definitions
Beta-glucans
Glucose polymers consisting of a backbone of beta(1->3)-linked beta-D-glucopyranosyl units with beta(1->6) linked side chains of various lengths. They are a major component of the CELL WALL of organisms and of soluble DIETARY FIBER.
Polyphosphates
Linear polymers in which orthophosphate residues are linked with energy-rich phosphoanhydride bonds. They are found in plants, animals, and microorganisms.
Polymers
Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).
Styrenes
Derivatives and polymers of styrene. They are used in the manufacturing of synthetic rubber, plastics, and resins. Some of the polymers form the skeletal structures for ion exchange resin beads.
Enhancer Elements, Genetic
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
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