Wanessa Silva Garcia Medina

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Topical photodynamic therapy (PDT) has been applied to almost all types of nonmelanoma skin cancer and numerous superficial benign skin disorders. Strategies to improve the accumulation of photosensitizer in the skin have been studied in recent years. Although the hydrophilic phthalocyanine zinc compound, zinc phthalocyanine tetrasulfonate (ZnPcSO4) has shown high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain tumors and eye conditions, its use in topical skin treatment is currently limited by its poor skin penetration. In this study, nanodispersions of monoolein (MO)-based liquid crystalline phases were studied for their ability to increase ZnPcSO4 uptake by the skin. Lamellar, hexagonal and cubic crystalline phases were prepared and identified by polarizing light microscopy, and the nanodispersions were analyzed by dynamic light scattering. In vitro skin penetration studies were performed using a Franzs cell apparatus, and the skin uptake was evaluated in vivo in hairless mice. Aqueous dispersions of cubic and hexagonal phases showed particles of nanometer size, approximately 224 ±10 nm and 188 ± 10 nm, respectively. In vitro skin retention experiments revealed higher fluorescence from the ZnPcSO4 in deeper skin layers when this photosensitizer was loaded in the hexagonal nanodispersion system when compared to both the cubic phase nanoparticles and the bulk crystalline phases (lamellar, cubic and hexagonal). The hexagonal nanodispersion showed a similar penetration behavior in animal tests. These results are important findings, suggesting the development of MO liquid crystal nanodispersions as potential delivery systems to enhance the efficacy of topical PDT.

Evaluation of critical parameters for in vitro skin permeation and penetration studies using animal skin models

ABSTRACT In vitro skin permeation/penetration studies may be affected by many sources of variation. Herein, we aimed to investigate the major critical procedures of in vitro skin delivery studies. These experiments were performed with model drugs according to official guidelines. The influence of skin source on penetration studies was studied as well as the use of a cryopreservation agent on skin freezing evaluated by transepidermal water loss, electrical resistance, permeation/penetration profiles and histological changes of the skin. The best condition for tape stripping procedure was validated through the evaluation of the distribution of corneocytes, mass of stratum corneum (SC) removed and amount of protein removed using finger pressure, a 2 kg weight and a roller. The interchangeability of the tape stripping procedures followed by the epidermis and dermis homogenate and the micrometric horizontal cryostat skin sectioning methods were also investigated, besides the effect of different formulations. Noteworthy, different skin sources were able to ensure reliable interchangeability for in vitro permeation studies. Furthermore, an increased penetration was obtained for stored frozen skin compared to fresh skin, even with the addition of a cryoprotectant agent. The best method for tape stripping was the finger pressure followed by the addition of a propylene glycol solvent leading to better SC removal. Finally, no significant difference was found in skin penetration studies performed by different methods suggesting their possible interchangeability. Graphical abstract Figure. No Caption available.

Nanocarriers to Deliver Photosensitizers in Topical Photodynamic Therapy and Photodiagnostics

Topical photodynamic therapy is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically approved indications have been restricted to superficial basal cell carcinoma and nodular, actinic keratoses and, since 2006, Bowen’s disease. Most photosensitizers are relatively hydrophobic and will be attracted to membranes, but even the exception molecules, having substituents that render them watersoluble, bind to membranes because of their hydrophobic ring systems. The primary function of the skin, however, is to protect the body from unwanted influences from the environment. This protection is provided primarily by the stratum corneum, which consists of corneocytes surrounded by lipid regions. The major limitation of PDT is the poor penetration of photosensitizers through biological barriers, like the skin. Over the past 10 years, a considerable number of studies have therefore been conducted on the development of different strategies to overcome these difficulties, including nanocarriers to delivery photosensitizers and their precursors, nanoemulsions, liposomes, ethosomes, invasomes, liquid crystals and magnetic nanoparticles, among others.

Current aspects of breast cancer therapy and diagnosis based on a nanocarrier approach

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide. Chemotherapy against breast carcinoma cells using nanocarriers directed to tumors is known as targeted therapy, and it provides a more specific therapy against cancer cells at the molecular level. Therefore, the use of nanocarriers is an advantageous therapeutic approach when compared to other cancer therapeutics. Over the years, it has become an enabling technology with potential for personalized cancer therapy, in which cancer cell detection, diagnosis, and therapy could be tailored to each individual tumors molecular profile because specific biomarkers could be used to predict disease progression and clinical outcomes. Here, we review nanosystems containing anticancer agents that are used for metastatic breast cancer in clinical practice, clinical trials, and research orientations. We also provide an overview of biomarkers used in metastatic breast cancer allowing for improved prognosis and therapy.

Characterization of Topical Delivery System of ZnPcSO 4 to Use in Photodynamic Therapy of Skin Cancer

We developed a nanodispersion system using Zinc Phtalocyanine Tetrasulphonet for photodynamic therapy. The characterization was performed based on liquid crystalline phases and photostability. We conclude that the method for preparation of nanodispersion was accomplished successfully.