ABSTRACT
Capsaicin (CP), a recent FDA-approved drug for the topical treatment of neuropathic pain, is associated with several side effects like irritation, burning sensation, and erythema, resulting in poor patient compliance. The present study is an attempt to study the effect of CP encasement in nano-lipoidal carriers (NLCs) on skin-transport characteristics, in vivo pharmacological performance, skin compliance, and stability of the finished product. The study also compares two methods of NLC preparation, namely microemulsification and rotary-evaporation for various attributes. The results demonstrated that microemulsion technique produced smaller nanoparticles vis-à-vis the rotary-evaporation method. Out of the various studied solid lipids, NLCs from stearic acid offered smallest size and the highest negative zeta potential. The NLC-gel offered higher skin permeation and skin retention of CP across LACA mice skin as compared with the conventional cream. The analgesic effect was observed to be enhanced substantially than that of the conventional cream when tested on a radiant mouse tail-flick model. The most alarming problems of skin-irritation and redness were successfully taken care by NLC-gel while the mice group receiving conventional cream showed marked changes in the skin histopathology. Besides the enhanced efficacy and decreased skin-irritation, the developed CP-NLCs also found to be stable and rheologically accepted formulation for the treatment of pain-associated disorders.
Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Capsaicin/administration & dosage , Drug Carriers/administration & dosage , Nanostructures/chemistry , Administration, Cutaneous , Analgesics, Non-Narcotic/adverse effects , Analgesics, Non-Narcotic/metabolism , Analgesics, Non-Narcotic/therapeutic use , Animals , Capsaicin/adverse effects , Capsaicin/metabolism , Capsaicin/therapeutic use , Colloids , Drug Carriers/adverse effects , Drug Carriers/metabolism , Drug Carriers/therapeutic use , Drug Compounding , Female , In Vitro Techniques , Liposomes , Mice , Skin/drug effects , Skin/metabolism , Skin AbsorptionABSTRACT
Isotretinoin (ITR) is a drug of choice in the treatment of all types of acne, including recalcitrant, severe and nodulocystic. The most widely employed route of its administration, i.e., oral intake, is reported to be associated with severe side-effects including teratogenecity, skin dryness and psychological disorders. Topical delivery, though advised for ITR, is marked with several hiccups like irritation, erythema and peeling of skin. The current studies, therefore, were embarked upon to develop "optimized" SLNs of ITR employing formulation by design (FbD) approach. The developed system was characterized and evaluated for skin compliance, skin transport characteristics and anti-acne potential against testosterone-induced acne in male Laca mice. The SLNs were able to transport the drug to various skin layers effectively while formed drug micro-reservoirs. The nano-colloidal systems showed marked anti-acne potential and tolerability on the mouse skin vis-à-vis the marketed product. The optimized SLNs exhibited drug entrapment of 89.49±4.1%, while the size was found to be in the nano-range (i.e., 75.3±2.4 nm). The ITR formulation was found to be stable too as per ICH guidelines. The results vouch immense promise of the optimized SLNs of ITR in reducing dermal irritation and increasing the therapeutic performance, thus resulting in an efficacious and patient-compliant formulation.
Subject(s)
Acne Vulgaris/drug therapy , Erythema/drug therapy , Isotretinoin/pharmacology , Lipids/chemistry , Nanoparticles/chemistry , Acne Vulgaris/chemically induced , Administration, Cutaneous , Androgens/toxicity , Animals , Drug Delivery Systems , Erythema/chemically induced , Isotretinoin/chemistry , Male , Materials Testing , Mice , Mice, Inbred Strains , Testosterone/toxicityABSTRACT
BACKGROUND: Treatment of photoaging includes non-prescription cosmeceuticals and prescription products, retinoids. Isotretinoin, an established anti-acne retinoid, is also reported to delay the aging process. However, the drug is reported to be an irritant on skin. PURPOSE: The present study endeavors to explore the potential of a novel set of biocompatible nano-structured systems of isotretinoin in the treatment of photoaging. METHODS: Nano-lipoidal carriers (NLCs) of isotretinoin were developed, characterized and investigated in vivo for anti-aging potential in Laca mice vis-à-vis the marketed products of retinoids. The anti-aging efficacy of NLCs was measured in terms of visual and redox-biochemical parameters in ultraviolet (UV)-irradiated mice. RESULTS: Visual observations revealed that there was no significant change (p < 0.05) w.r.t. erythema, skin sagging and wrinkles in the skin of the animals treated with NLCs formulation compared to the marketed product(s). The malondialdehyde levels were found to be significantly reduced, whereas glutathione levels were increased with the application of NLCs vis-à-vis control and test formulations. The NLCs were able to maintain the normal redox-balance of UV-irradiated skin, and were better tolerated by the animals. CONCLUSION: The study ratifies enhancement in the efficacy of isotretinoin against photoaging and improved skin biocompatibility after its encasement in novel topical dosage forms.