Development of percutaneous drug delivery by protein transduction domain

Development of percutaneous drug delivery by protein transduction domain

P1021 P1023 DEVELOPMENT OF PERCUTANEOUS DRUG DELIVERY BY PROTEIN TRANSDUCTION DOMAIN Joon Seo, MD, Department of Dermatology, College of Medicine, C...

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P1023

DEVELOPMENT OF PERCUTANEOUS DRUG DELIVERY BY PROTEIN TRANSDUCTION DOMAIN Joon Seo, MD, Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea; Seungkye Lee, PhD, Forhuman Tech, Korea; Jeunghoon Lee, MD, Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea

EFFECTS OF 10 KINDS OF CHINESE MEDICINAL HERBS AND PLANT EXTRACTS ON VEGF SECRETION OF KERATINOCYTES X. Zh. Yue, MD, W. Y. Zhu, MD, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; P. W. Sun, PhD, Procter & Gamble Company, Kobe, Japan

Protein transduction doman (PTD) is a new kind of drug delivery system capable of delivering high molecular weight drugs into the cells and is composed of several amino acid chains. We found and now have two PTDs (MPH-1, SIM-2). With these, we synthesized PTD-FITC (high molecular weight macromolecules) conjugate, PTDb-gal conjugate, and observed intracellular penetration of these molecules faster than FITC or b-gal alone in cellular and animal models. Using this nanotechnique, development of new topical drugs or recycling of drugs, which are previously proven ineffective on topical application because of hydrophilicity, high molecular weight, among others, may be possible. We are now searching for target molecules appropriate for conjugation with PTD, such as PTD-methotrexate or PTD-antiapoptotic agents. Nothing to disclose.

Introduction: Skin blood vessels are a complex dynamic system. They are essential to supply sufficient oxygen and nutrients to the skin to maintain normal tissue homeostasis and function. They also have an important role in determining skin color. However, the skin superficial blood vessels decrease significantly with aging, contributing to the paler, more sallow color of older skin. Recently, Detmar et al have confirmed the in vivo biological importance of epidermal-derived vascular endothelial growth factor (VEGF) for cutaneous angiogenesis in a transgenic mouse model. Angiogenesis also plays a central role in wound healing. VEGF is mainly produced by keratinocytes in the epidermis and is believed to be the most prevalent, potent, and long-term signal that is known to stimulate angiogenesis. Objective: To observe effects of 10 kinds of extracts of Chinese medicinal herbs and plants on VEGF secretion of keratinocytes. Materials and methods: Ten kinds of extracts of Chinese medicinal herbs and plants were studied. Cultured keratinocytes (HaCaT cell line) were used as an in vitro model. Different concentrations of extracts were tested for cytotoxic activity on HaCaT cells using the 3-(4, -dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. The level of VEGF in culture supernatant fluid was measured by ELISA kits. Results: Of the 10 kinds of extracts, only flavonoid can increase the secretion of VEGF significantly. The VEGF secretion level of the flavonoid group is twice that of the control group. Conclusion: The present study revealed that flavonoid can induce HaCaT cells to significantly produce VEGF. This material may have potential utility in wound healing and in improving the blood flow in older skin, resulting in less sallow appearance. 100% supported by The Procter & Gamble Company

P1024

DOCUMENTATION OF CUTANEOUS CONDITIONS IMPORTANT IN SKIN OF COLOR WITH INNOVATIVE IMAGING APPROACHES Warren Wallo, MS, Jacqueline Woodruff, BS, Geoffrey Smith, BS, Ellen S. Kurtz, PhD, Johnson & Johnson Consumer & Personal Products Worldwide, Skillman, NJ, United States Certain skin conditions that are extremely important to patients with skin of color have traditionally been difficult to document in the clinical setting. Postinflammatory hyperpigmentation (PIH) is characterized by variations in the distribution and intensity of skin pigmentation components. This is especially problematic in skin of color because the melanocytes are very active and lead to dark marks wherever inflammation or a trauma has occurred. Pseudofolliculitis barbae (PFB) is a painful condition commonly affecting the majority of adult African American men. The morphology of the hair in these patients is prone to curving and penetrating the cutaneous surface after shaving. Subsequent formation of inflammatory papules and pustules can result in hypertrophic lesions as a result of the foreign body reaction to the ingrown hair. We have utilized new high-resolution digital imaging techniques employing videomicroscopy and epiluminescence microscopy to document these conditions in the clinic and to accurately monitor significant changes over time. It has been demonstrated that the size and intensity of PIH marks can be documented over time with excellent digital image quality. Observations of extrafollicular penetration, one of the previously identified mechanisms for PFB, were clinically demonstrated with extremely high detail. These techniques provide the clinician with the ability to accurately document patient skin conditions and to monitor treatments and procedures that improve these conditions on both the face and body in their patients with skin of color.

EFFECTS OF AN SPF 15 MOISTURIZER CONTAINING ANTIOXIDANTS ON CELLULAR PROTECTION OF SKIN AGAINST UV IRRADIATION AND POLLUTANTS Theresa Chen, PhD, Neutrogena Skincare Institute, Los Angeles, CA, United States; Claude Saliou, PhD, Johnson & Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United States; Monya Sigler, PhD, Thomas J. Stephens and Associates, Carrollton, TX, United States; Roderico Estanislao, BSc, Johnson & Johnson (Philippines), Inc., Manila, Philippines The skin is constantly exposed to UV rays and pollution. Both lead to the induction of cellular damage and inflammatory response, which has been proven to be at least partly responsible for epidermal and dermal matrix degradation. Hence there is a need for skin protectors that can attenuate the destructive effects of these aggressors. A combination of UVA/UVB sunscreens and an antioxidant blend in a moisturizing base was developed and tested for its ability to prevent skin cell damages caused by exposures to UV and air pollutants. In situ studies of exposing human epidermal equivalents to solar UV light and cigarette smoke (as a representative of air pollution) showed that the combination of sunscreens and antioxidants was most effective in protecting skin cells against UV and cigarette smoke by reducing cellular inflammation and apoptosis, the sunscreens alone were a close second, and antioxidant blend was better than placebo. Next, two investigatorblinded, randomized, clinical studies were conducted to evaluate the in vivo potency of the sunscreens and antioxidant combination. The first study was conducted with antioxidants alone, and with placebo, in subjects (18-60 years of age) with Fitzpatrick skin types II and III on the skin of the back by patching the test materials for 5 days. The combination of sunscreens and antioxidants again showed the best anti-UV efficacy with little or no UV-induced erythema, color darkening, and sunburn cell formation. Antioxidants alone showed somewhat less sunburn cell formation, erythema, color darkening, and transepidermal water loss than the placebo. Antioxidants alone also increased the minimal erythema dose (MED) of the skin. The second study, a double-blind, randomized, clinical study on Fitzpatrick type IV to V Asian skin, showed that continued use of the same moisturizer with combination of sunscreens and antioxidants can provide significant visible improvement in the appearance of facial skin, particularly hyperpigmentation, fine lines and wrinkles, overall fairness, roughness and sallowness, thus helping to mitigate the effects of UV damage. Together, these results showed that the combination of sunscreens and antioxidants in the test moisturizer base offer superior protection against UV and pollution.

The authors are employees of Johnson & Johnson Consumer & Personal Products Worldwide, Division of Johnson & Johnson Consumer Companies, Inc. 100% sponsored by Johnson & Johnson Consumer & Personal Products Worldwide, Division of Johnson & Johnson Consumer Companies, Inc.

The authors are either employed by or under contract to Neutrogena Corporation and its affiliate, Johnson & Johnson Consumer and Personal Products Worldwide. 100% sponsored by Neutrogena Corporation and Johnson & Johnson (Philippines) Inc.

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MARCH 2005

J AM ACAD DERMATOL

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