ABSTRACT
This study investigates the potential application of polymeric nanospheres (known as TyroSpheres) as a formulation carrier for topical delivery of cholecalciferol (i.e., Vitamin D3, VD3) with the goal to improve the skin delivery and stability of VD3. High drug loading and binding efficiencies were obtained for VD3 when loaded in TyroSpheres. VD3 was released from TyroSpheres in a sustained manner and was delivered across the stratum corneum, which occurred independent of the initial drug loading. An ex vivo skin distribution study showed that TyroSphere formulations delivered 3-10µg of active into the epidermis which was significantly higher than that delivered from Transcutol® (the control vehicle). In addition, an in vitro cytotoxicity assay using keratinocytes confirmed that VD3 encapsulation in the nanoparticles did not alter the drug activity. Photodegradation of VD3 followed zero-order kinetics. TyroSpheres were able to protect the active against hydrolysis and photodegradation, significantly enhancing the stability of VD3 in the topical formulation.
Subject(s)
Cholecalciferol/administration & dosage , Drug Delivery Systems , Nanospheres , Polymers/chemistry , Administration, Cutaneous , Cell Line , Chemistry, Pharmaceutical/methods , Cholecalciferol/pharmacokinetics , Delayed-Action Preparations , Drug Liberation , Drug Stability , Humans , Keratinocytes/metabolism , Male , Photolysis , Skin/metabolism , Skin AbsorptionABSTRACT
A potential topical psoriasis therapy has been developed consisting of tyrosine-derived nanospheres (TyroSpheres) with encapsulated anti-proliferative paclitaxel. TyroSpheres provide enhancement of paclitaxel solubility (almost 4000 times greater than PBS) by effective encapsulation and enable sustained, dose-controlled release over 72 h under conditions mimicking skin permeation. TyroSpheres offer potential in the treatment of psoriasis, a disease resulting from over-proliferation of keratinocytes in the basal layer of the epidermis, by (a) enabling delivery of paclitaxel into the epidermis at concentrations >100 ng/cm(2) of skin surface area and (b) enhancing the cytotoxicity of loaded paclitaxel to human keratinocytes (IC(50) of paclitaxel-TyroSpheres was approximately 45% lower than that of free paclitaxel). TyroSpheres were incorporated into a gel-like viscous formulation to improve their flow characteristics with no impact on homogeneity, release or skin distribution of the payload. The findings reported here confirm that the TyroSpheres provide a platform for paclitaxel topical administration allowing skin drug localization and minimal systemic escape.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Drug Carriers/administration & dosage , Nanospheres/administration & dosage , Paclitaxel/administration & dosage , Administration, Cutaneous , Antineoplastic Agents, Phytogenic/chemistry , Cell Line , Drug Carriers/chemistry , Humans , Nanospheres/chemistry , Paclitaxel/chemistry , Skin/metabolism , Skin Absorption , TyrosineABSTRACT
Quartz crystal microbalance (QCM) with dissipation can be used to measure the response of the human stratum corneum (SC) attached to the QCM crystal, as it adsorbs or desorbs active ingredients from a liquid medium. The method was demonstrated with the sorption of poly(diallyl dimethyl ammonium chloride), a cationic polymer widely used in formulations for topical and transdermal applications. Using 14-mm diameter SC coupons attached to the QCM crystals with an adhesive, up to five overtones (up to 11th harmonic) were obtained and the response was analyzed using a Voigt model. The adhesive layer could be regarded as a rigid substrate, and the skin with overlaying fluid was modeled as a soft layer underneath a fluid medium. Limited modeling tools that are currently available were used to interpret the observed response in terms of physical parameters such as the changes in thickness, shear modulus, and viscosity. The high sensitivity of the technique demonstrates the possibility of using small samples of human skin for in vitro studies in a variety of topical and transdermal drug delivery applications and in the evaluation of skin care products.
