PLGA nanoparticles as delivery systems for protoporphyrin IX in topical PDT: cutaneous penetration of photosensitizer observed by fluorescence microscopy.

Poly(D,L lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) are proposed for topical delivery of Protoporphyrin IX (PpIX) in Photodynamic Therapy of skin cancers. PpIX loaded into PLGA NPs showed nanometric average diameter (-280 nm), spherical forms and pH - 5.7, conditions suitable for topical application. In vitro release of PpIX from NPs was sustained up to 24 hr with a burst release effect of about 37.0% at 2 hr. Penetration and distribution of PpIX in hairless mice skin was determined by fluorescence microscopy 8 or 24 hrs after application of PpIX-NPs in the animals. At 24 hours, areas located in deeper regions of the skin were found to have greater fluorescence intensity. The finding indicates a localized effect of PpIX-NPs in the epidermis plus dermis--a site of action for topical PDT--and suggests a potential use of PpIX-NPs in PDT associated to skin cancer treatments.

Current Applications and Benefits of Polymeric Nanocarriers for the Management of Skin Disorders.

Preparations for topical application are highly important for therapeutic and cosmetic use since the skin has an extensive and accessible application area. Among the many advantages, this route avoids the systemic effects of the substances and, therefore, fewer adverse reactions are observed. However, the skin is an organ with a remarkable barrier effect, which can compromise the administration of pharmacologically / cosmetologically active molecules. Thus, the skin permeability of substances is a challenge that is only achieved through the preparation of formulations capable of overcoming that same barrier. Nanotechnology was introduced in the pharmaceutical and cosmetic areas to enable the development of systems for the delivery of substances and the optimization of already existing formulations. Among the several benefits and advantages of nanotechnology for topical application is the increased penetration of the drug in the skin, the improvement of the stability of the active, decrease in the active substances (reducing the possible toxic effects and allergic reactions caused by the high concentration of these compounds), and even the intensification of the drug action. This manuscript reviews the topical delivery technologies based on polymeric nanocarriers (PNC) as nanoparticles (NP) and nanogels (NG) and their benefits for better efficacy in most common cutaneous disorders. It starts with skin properties, the aspects for the penetration of active ingredients in the skin and cutaneous penetration challenges, followed by a summary of strategies for skin penetration/permeation of drugs. Then, the focus of the current research was to review NPs and NGs explored for skin disorders management published during the last years.

Influence of oleic acid on the rheology and in vitro release of lumiracoxib from poloxamer gels.

PURPOSE: Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to avoid the side effects associated with systemic delivery, but it is ineffective due to the drug poor skin penetration. We have investigated the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro release of LM from poloxamer-based delivery systems (PBDS). The rheological behavior (shear rate dependent viscosity) and gelation temperature through measurements of optimal sol-gel transition temperatures (Tsol-gel) were also carried out in these systems. METHODS: In vitro release studies of LM from PBDS were performed using cellulose acetate as artificial membrane mounted in a diffusion system. The amount of LM released was divided by exposition area (microg/cm2) and these values were plotted as function of the time (h). The flux of the drug across the membrane (J) was calculated from the slope of the linear portion of the plot and expressed as microg/cm2. h -1. The determination of viscosity was carried out at different shear rates (gamma) between 0.1- 1000 S-1 using a parallel plate rheometer. Oscillatory measurements using a cone-plate geometry rheometer surrounded by a double jacket with temperature varying 4-40 degrees C, was used in order to determine Tsol-gel. RESULTS: Increase of both polymer and OA concentrations increases the viscosity of the gels and consequently reduces the in vitro LM release from the PBDS, mainly for gels containing OA at 10.0% compared to other concentrations of the penetration enhancer. Tsol-gel transition temperature was decreased by increasing viscosity; in some cases the formulation was already a gel at room temperature. Rheological studies showed a pseudoplastic behavior, which facilitates the flow and improves the spreading characteristics of the formulations. CONCLUSIONS: Taken together, the results showed that poloxamer gels are good potential delivery systems for LM, leading to a sustained release, and also have appropriate rheological characteristics. Novelty of the work: A transdermal delivery of non-steroidal antinflammatory drugs like lumiracoxib (LM) can be an interesting alternative to the oral route of this drug, since it was recently withdraw of the market due to the liver damage when systemically administered in tablets as dosage form. There are no transdermal formulations of LM and it could be an alternative to treat inflammation caused by arthritis or arthrosis. Then, an adequate delivery system to LM is necessary in order to release the drug properly from the PBDS as well as have good characteristics related to semi-solid preparations for transdermal application, which were evaluated through in vitro release studies and rheological behavior in this paper, respectively.

Liposomal systems as drug delivery vehicles for dermal and transdermal applications.

Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs applied to the skin due to its amazing barrier, the stratum corneum. Strategies to overcome this barrier, thus improving drug release to the skin include the use of penetration enhancers, specific delivery systems, supersaturated solutions and physical methods (iontophoresis, electroporation and ultrasound). Delivery of active agents to the skin by liposomal carriers has improved topical therapy in the field of dermatology. The interest in these carriers is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Particularly, in recent years liposomes have been shown to be a promising drug-delivery system to the skin. Their use may produce several-fold higher drug concentrations in the epidermis and dermis and lower systemic concentrations when compared to conventional dosage forms. On the other hand, special characteristic vesicles like ethosomes, transfersomes and niosomes may be potential transdermal delivery systems for ionic molecules and polypeptides.