Perspective in Topical Infective and Non-infective Skin Diseases Therapy with Emergence of Nanomedicine.

Abstract

The current crisis of skin infections caused by a wide range of bacteria, fungi and virus has resulted in an exponential increase in morbidity [1, 2]. Despite the recent advancements in dermatological treatments, the treatment of topical infections has always been a difficult proposition because of the lack of efficacy of existing formulations, longer period of treatment and yet incomplete recovery. Implication of various microbes like Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Gram-positive, Gram-negative bacteria and fungi is causing complex problems [3]. Moreover, the severity of the problem also depends on the structure of skin layers and the target site. Although, the defensive properties of skin like acidic pH and significant antibacterial activity exhibited by its constituent components like Lauric acid and palmitoleic acid encompass the anti-infective mechanism against topical infections [4], however, in certain conditions like burns, wounds and diabetes mellitus, skin loses its defense mechanism with the entry of pathogens followed by the development of infection. Further, its barrier nature presents an arduous impediment for most drugs to be delivered into and through it owing to the prevailing patho-physiological conditions [5]. Besides, the drug’s intrinsic physico-chemical characteristics viz. pKa, molecular size, stability, binding affinity, solubility and partition coefficient remain unfavorable for drug delivery across the skin barrier [6-8]. Human beings are the natural hosts for many bacterial pathogens that colonize the skin as normal flora. Staphylococcus aureus and Streptococcus pyogenes account for a wide variety of bacterial infections. A wide variety of bacterial infections affect the normal physiology of skin including cellulitis, folliculitis, impetigo, carbuncle and furuncle. The predisposing factors to infection include minor trauma, pre-existing skin disease, poor hygiene, and rarely, impaired host immunity. Cellulitis is a superficial bacterial infection of the lower dermis and upper subcutaneous tissue frequently affecting the legs. The major causative organism of cellulitis is Group A beta-hemolytic Staphylococcus aureus along with other microbes like Pseudomonas aeruginosa, Escherichia coli and Klebsiella species [9]. Impetigo is a superficial cutaneous infection resulting from the direct invasion of healthy tissues, or occurs secondarily to an underlying skin disease especially around nose, mouth and wounds. It occurs in patients already exposed to eczema and diabetes caused mainly by Staphylococcus aureus and Staphylococcus pyogens [10]. Folliculitis is a cutaneous infection of the hair follicles such as the scalp, neck, beard area, axillae, buttocks and limbs characterized by follicular-based pustules. Carbuncles show inflamed skin and pus drainage from hair follicles [10]. The treatment strategies for bacterial skin infections include dicloxacillin, clavulanic acid, amoxicillin, erythromycin, clindamycin and vancomycin. Fungal and yeast topical infections include dermatophytosis, pityriasis versicolor and candidiasis. Dermatophytosis implies an infection caused due to Trichophyton rubrum, having high affinity for the keratinized tissue such as skin, hair and nails. The other prevalent type of fungal skin infection is caused by Candida species, namely Candida albicans. These include candida vulvovaginitis, intertrigo (skin fold infections), napkin dermatitis, chronic paronychia (nail fold infection) and onychomycosis (nail plate infection) [10]. Tinea versicolor is an opportunistic infection caused by yeast Malasezzia furfur. Tinea pedis affects the feet with scaling plaques on the soles. Tinea capitis is characterized by scaly, erythematous skin with hair loss. The treatment strategies for fungal topical infections include terbinafine, clotrimazole, econazole, fluconazole, ketoconazole and itraconazole [10]. Herpes simplex (HSV), Herpes zoster, Molluscum contagiosum, Erythema infectiosum, Roseola infantum, Herpes simplex and chicken pox are some of the viral topical infections. HSV infection is painful and characterized by grouped vesicles along with dermatitis. HSV I is associated with orofacial disease and HSV II with genital infection [10]. Molluscum contagiosum spreads by the direct contact and is caused by benign pox virus. Herpes zoster (shingles) is an acute, painful dermatitis in the presence of immunosuppression. The common treatment strategies for viral infections include acyclovir, valacyclovir and imiquimod.