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Yoctowells as a simple model system for the encapsulation and controlled release of bioactive molecules.

ABSTRACT: The development of nanosized drug delivery systems to transport drugs to target cells, are promising tools to improve the drug therapeutic index. Transport systems should have a simple design to control the release of loaded drug to the target areas, thereby increasing concentration and prolonging retention. Herein, we demonstrate the use of yoctoliter wells (1?yL = 10(-24)?L) as simple model systems for the encapsulation and release of biologically active molecules, by manipulating pH. The drug molecule employed here is doxorubicin, which diffuses into the bottom of yoctowells from a bulk solution at pH 7. Capping of the yoctowells is achieved by addition of an anionic-porphyrin by electrostatic interaction. Furthermore, controlled release of the Doxorubcin and capping agent from the yoctowells is achieved by pH control. The effectiveness of the sustain release of the bioactive molecule from yoctowells, provides potential for development of a new generation of drug-delivery system for practical application.

SUBMITTER: Bhosale SV

PROVIDER: S-EPMC3683640 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Yoctowells as a simple model system for the encapsulation and controlled release of bioactive molecules.

Bhosale Sheshanath V SV Bhosale Sidhanath V SV

Scientific reports 20130101

The development of nanosized drug delivery systems to transport drugs to target cells, are promising tools to improve the drug therapeutic index. Transport systems should have a simple design to control the release of loaded drug to the target areas, thereby increasing concentration and prolonging retention. Herein, we demonstrate the use of yoctoliter wells (1 yL = 10(-24) L) as simple model systems for the encapsulation and release of biologically active molecules, by manipulating pH. The drug ...[more]

PMID: 23760359

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Project description:Hydrogel scaffolds are used in biomedicine to study cell differentiation and tissue evolution, where it is critical to control the delivery of chemical cues both spatially and temporally. While large molecules can be physically entrapped in a hydrogel, moderate molecular weight therapeutics must be tethered to the hydrogel network through a labile linkage to allow controlled release. We synthesized and characterized a library of polymerizable ortho-nitrobenzyl (o-NB) macromers with different functionalities at the benzylic position (alcohol, amine, BOC-amine, halide, acrylate, carboxylic acid, activated disulfide, N-hydroxysuccinyl ester, biotin). This library of polymerizable macromers containing o-NB groups should allow direct conjugation of nearly any type of therapeutic agent and its subsequent controlled photorelease from a hydrogel network. As proof-of-concept, we incorporated the N-hydroxysuccinyl ester macromer into hydrogels and then reacted phenylalanine with the NHS ester. Upon exposure to light (? = 365 nm; 10 mW/cm(2), 10 min), 81.3% of the phenylalanine was released from the gel. Utilizing the photodegradable macromer incorporating an activated disulfide, we conjugated a cell-adhesive peptide (GCGYGRGDSPG), a protein that exhibits enzymatic activity (bovine serum albumin (BSA)), and a growth factor (transforming growth factor-?1 (TGF-?1)) into hydrogels, controlled their release with light (? = 365 nm; 10 mW/cm(2), 0-20 min), and verified the bioactivity of the photoreleased molecules. The photoreleasable peptide allows real-time control over cell adhesion. BSA maintains full enzymatic activity upon sequestration and release from the hydrogel. Photoreleased TGF-?1 is able to induce chondrogenic differentiation of human mesenchymal stem cells comparable to native TGF-?1. Through this approach, we have demonstrated that photodegradable tethers can be used to sequester peptides and proteins into hydrogel depots and release them in an externally controlled, predictable manner without compromising biological function.

Dataset Information

Yoctowells as a simple model system for the encapsulation and controlled release of bioactive molecules.

Publications

Yoctowells as a simple model system for the encapsulation and controlled release of bioactive molecules.

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