Optimization of rapamycin-loaded acetalated dextran microparticles for immunosuppression.
Summary of "Optimization of rapamycin-loaded acetalated dextran microparticles for immunosuppression."
Immunosuppressive drugs can treat autoimmune disorders and limit rejection with organ transplants. However, delivering immunosuppressants like rapamycin systemically can have harmful side-effects. We aim to potentially reduce these toxic side-effects by encapsulating rapamycin in a polymeric microparticle to passively target phagocytes, the cells integral in immunosuppression. Acetalated dextran (Ac-DEX) is a recently described, biocompatible polymer which undergoes tunable burst degradation at the acidic conditions present in the phagosome (pH 5) but slower degradation at extracellular conditions (pH 7.4), thereby making it an ideal candidate for immune applications. Rapamycin-loaded microparticles were fabricated from Ac-DEX through a single emulsion (water/oil) technique. Optimized microparticles were determined by varying the chemical and physical parameters during particle synthesis. Microparticles synthesized from Ac-DEX with a molecular weight of 71k had higher encapsulation efficiency of rapamycin and slower overall degradation than microparticles synthesized from 10k Ac-DEX. To evaluate the ability of rapamycin-loaded Ac-DEX microparticles to reduce a pro-inflammatory response, they were incubated with lipopolysaccharide-stimulated RAW macrophages. RAW macrophages treated with rapamycin-loaded microparticles exhibited reduced nitric oxide production and favorable cell viability. Overall, we have shown optimization of immunosuppressive rapamycin-loaded microparticles using the novel polymer Ac-DEX. These particles will be advantageous for future applications in immune suppression therapies.
Affiliation
William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, United States.
Journal Details
This article was published in the following journal.
Name: International journal of pharmaceutics
ISSN: 1873-3476
Pages: 356-63
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22037446
- DOI: http://dx.doi.org/10.1016/j.ijpharm.2011.10.034
Medical and Biotech [MESH] Definitions
Cell-derived Microparticles
Extracellular membrane vesicles generated by the shedding of CELL MEMBRANES blebs. Microparticles originating from PLATELETS; ENDOTHELIAL CELLS; and other cell types circulate in the peripheral blood and through the MICROVASCULATURE where larger cells cannot, functioning as active effectors in a variety of vascular processes such as INFLAMMATION; HEMOSTASIS; angiogenesis; and vascular reactivity. Increased levels are found following stimulation of bleb formation under normal or pathological conditions.
Tor Serine-threonine Kinases
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
Deae-dextran
Used as a support for ion-exchange chromatography.
Film Dosimetry
Use of a device (film badge) for measuring exposure of individuals to radiation. It is usually made of metal, plastic, or paper and loaded with one or more pieces of x-ray film.
Opportunistic Infections
An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.
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