Enhanced Drug Delivery to the Skin Using Liposomes.


Enhancing drug delivery to the skin has importance in many therapeutic strategies. In particular, the outcome in vascularized composite allotransplantation mainly depends on systemic immunosuppression to prevent and treat episodes of transplant rejection. However, the side effects of systemic immunosuppression may introduce substantial risk to the patient and are weighed against the expected benefits. Successful enhancement of delivery of immunosuppressive agents to the most immunogenic tissues would allow for a reduction in systemic doses, thereby minimizing side effects. Nanoparticle-assisted transport by low temperature-sensitive liposomes (LTSLs) has shown some benefit in anticancer therapy. Our goal was to test whether delivery of a marker agent to the skin could be selectively enhanced.In an in vivo model, LTSLs containing doxorubicin (dox) as a marker were administered intravenously to rats that were exposed locally to mild hyperthermia. Skin samples of the hyperthermia treated hind limb were compared with skin of the contralateral normothermia hind limb. Tissue content of dox was quantified both via high-performance liquid chromatography and via histology in skin and liver.The concentration of dox in hyperthermia-treated skin was significantly elevated over both normothermic skin and liver. (P < 0.02).We show here that delivery of therapeutics to the skin can be targeted and enhanced using LTSLs. Targeting drug delivery with this method may reduce the systemic toxicity seen in a systemic free-drug administration. Development of more hydrophilic immunosuppressants in the future would increase the applicability of this system in the treatment of rejection reactions in vascularized composite allotransplantation. The treatment of other skin condition might be another potential application.






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Publication Info

Blueschke, Gert, Alina Boico, Ayele H Negussie, Pavel Yarmolenko, Bradford J Wood, Ivan Spasojevic, Ping Fan, Detlev Erdmann, et al. (2018). Enhanced Drug Delivery to the Skin Using Liposomes. Plastic and reconstructive surgery. Global open, 6(7). p. e1739. 10.1097/GOX.0000000000001739 Retrieved from https://hdl.handle.net/10161/18475.

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Ivan Spasojevic

Associate Professor in Medicine

Detlev Erdmann

Professor of Surgery

Bruce Klitzman

Associate Professor Emeritus in Surgery

Our overriding interests are in the fields of tissue engineering, wound healing, biosensors, and long term improvement of medical device implantation. My basic research interests are in the area of physiological mechanisms of optimizing substrate transport to tissue. This broad topic covers studies on a whole animal, whole organ, hemorheological, microvascular, cellular, ultrastructural, and molecular level. The current projects include:
1) control of blood flow and flow distribution in the microcirculation,
2) the effects of long-term synthetic and biologic implants on substrate transport to tissues,
3) tissue engineering; combining isolated cells, especially adult stem cells, with biomaterials to form specialized composite structures for implantation, with particular emphasis on endothelial cell physiology and its alteration by isolation and seeding on biomaterials.
4) decreasing the thrombogenicity of synthetic blood vessels and other blood-contacting devices, and improving their overall performance and biocompatibility.
5) reducing tissue damage resulting from abnormal perfusion (e.g., relative ischemia, anoxia, etc.) and therapies which minimize ischemic damage.
6) biosensor function, particularly glucose sensors in normal and diabetics.
7) measurement of tissue blood flow and oxygenation as an indicator of tissue viability and functional potential.
8) development of biocompatible materials for soft tissue reconstruction or augmentation.
9) improving performance of glaucoma drainage devices by directing a more favorable foreign body reaction
10) wound healing; particularly internal healing around foreign materials and the effect and prevention of microbes around implanted devices.

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