Development of Nanoparticulate Delivery System for Wound Healing

Abstract

A new nanoparticulate delivery system will be tested as an alternative to other polymer carriers or liposomes for delivery (in the context of wound healing) of growth factors as well as for gene transfer and for endocytosis-mediated uptake of antisense messenger oligonucleotides. The application of this water-based and unique nanoparticulate system is novel (except for one application of another type of nantechnology for antisense delivery). TGF-beta1 has been chosen as a model factor because of its significance in the control of the would healing process and of the accumulated experience in the Co-Pl's laboratory. A controlled delivery growth factor itself, an incorporation of its expression cDNA (plasmid) as well as of TGF-beta1-specific antisense oligonucleotide will be attempted to increase TGF-beta1 levels or modulate its activity in cultures as well as in vivo. This proposal represents the first phase of a feasibility study to demonstrate the possibility of using this new delivery (and carrier) particulate system to arrive at pharmacologically significant quantities. A limited screening of different nanoparticulate chemistries will be attempted in order to arrive at a resuspendable (single) particulate system, applicable for an injectable delivery. A small size of the nanoparticulate system is an essential requirement for an efficient (non-viral) gene and antisense nucleotide incorporation.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Type: Center Core Grants (P30)
• Project #: 5P30AR041943-05
• Application #: 2779045
• Budget Start: 1997-10-01
• Budget End: 1998-09-30
• Support Year: 5
• Fiscal Year: 1998

Institution

• Name: Vanderbilt University Medical Center
• DUNS #: 004413456
• City: Nashville
• State: TN
• Country: United States
• Zip Code: 37212

Publications

Russell, Shirley B; Smith, Joan C; Huang, Minjun et al. (2015) Pleiotropic Effects of Immune Responses Explain Variation in the Prevalence of Fibroproliferative Diseases. PLoS Genet 11:e1005568

Velez Edwards, Digna R; Tsosie, Krystal S; Williams, Scott M et al. (2014) Admixture mapping identifies a locus at 15q21.2-22.3 associated with keloid formation in African Americans. Hum Genet 133:1513-23

Duncan, F Jason; Silva, Kathleen A; Johnson, Charles J et al. (2013) Endogenous retinoids in the pathogenesis of alopecia areata. J Invest Dermatol 133:334-43

Takahashi, Keiko; Mernaugh, Raymond L; Friedman, David B et al. (2012) Thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase. Proc Natl Acad Sci U S A 109:1985-90

Jandova, Jana; Eshaghian, Alex; Shi, Mingjian et al. (2012) Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry. J Invest Dermatol 132:421-8

Jandova, Jana; Shi, Mingjian; Norman, Kimberly G et al. (2012) Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype. Biochim Biophys Acta 1822:293-300

Sundberg, J P; Taylor, D; Lorch, G et al. (2011) Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans. Vet Pathol 48:513-24

Russell, Shirley B; Russell, James D; Trupin, Kathryn M et al. (2010) Epigenetically altered wound healing in keloid fibroblasts. J Invest Dermatol 130:2489-96

Norman, Kimberly G; Canter, Jeffrey A; Shi, Mingjian et al. (2010) Cyclosporine A suppresses keratinocyte cell death through MPTP inhibition in a model for skin cancer in organ transplant recipients. Mitochondrion 10:94-101

Harries, M J; Sun, J; Paus, R et al. (2010) Management of alopecia areata. BMJ 341:c3671