Investigating the cutaneous distribution of natural products and small molecules following topical application of formulations for dermatological indications
|Prof. Yogeshvar Kalia
|Résumé de la thèse
There is an increasing trend toward the use of plant-derived compounds due to their perceived “natural character” implying lower toxicity and increased biocompatibility . Many drugs and cosmetic products/cosmeceuticals are composed of or derived from plant mixtures because they contain chemo-diverse molecules (natural products (NP)) that may exhibit strong bioactivities. NP are being used for topical treatments of very common but different skin conditions, e.g. acne, wound healing, and hyperpigmentation. In terms of local application, their efficacy depends on the ability of the active molecule(s) to be transported across the stratum corneum (SC) and reach the desired target area (epidermis, upper or lower dermis). Due to their diverse constituents, little research has been conducted to understand which NP penetrate efficiently through the skin from a complex mixture and give rise to the pharmacological effect. In order to identify the active components, it is important to be able to monitor multiple compounds released from the plant mixture into the skin and to determine which ones reach the specific layer. To date, few models can be used to explore the bioavailability of NP applied on the skin and released from a complex mixture.
Besides the diversity of NP in plant mixtures, the preparation of topical formulations containing plant extracts or pure NP is challenging due to their physicochemical properties, which are mostly poorly water-soluble and have poor stability. Conventional formulations such as ointments and creams are not the best choices due to their high affinity for the active agent. To overcome those limitations, new drug carriers have been developed in this project, the focus will be on nano-emulsions and polymeric micelles.
To examine the ability of different formulations to enhance the skin deposition of a drug, our research group already developed a new method named the Cutaneous Biodistribution Method (CBM). This method was established to investigate the spatial biodistribution of low molecular weight drugs in the different skin layers as a function of depth. The purpose of my PhD project is to adapt this method to quantify NP, both as single molecules or when released from mixtures and to investigate the role of different formulations in improving the cutaneous deposition of NP.
In the first part of this project, Bakuchiol (BAK) and Rice Bran Oil (RBO) have been selected to represent the pure and complex mixtures of NP. BAK is a natural compound isolated from the Psoralea coryfolia L. plant that is being used nowadays as an alternative to retinol for anti-aging treatment. RBO is a vegetable oil extracted from the hard outer layer of rice and has been shown to be a potent antioxidant.
This part of my project can be divided into two different activities. The first is to formulate BAK-loaded polymeric micelles and to evaluate the skin biodistribution of BAK following the application of different micelles composed of different block copolymers. This will investigate how the nature of the polymer can impact on the cutaneous distribution profile. The second activity is the formulation of nano-emulsion containing RBO and investigating the skin distribution of several NP released from RBO using CBM.
These two parts will be executed in parallel. In summary, the aim of this PhD project is: (1) To show how the skin delivery of (i) a pure NP and (ii) of NP from complex mixtures, can be improved using using nano-formulation approaches, (2) To develop methods to monitor the skin penetration of pure NP and from complex plant mixtures – this will involve precise and validated analytical methods for quantifying pure NP and also untargeted methods to see how multiple components might be released from a formulation and how they are distributed within the skin (3) To adapt the CBM for understanding the spatial distribution of single NP and multiple components from complex plant mixtures in the skin. Thus, this initial approach using BAK and RBO will be the first proof-of-principle study to establish the method for investigating the cutaneous delivery of other complex mixtures of topical herbal preparations.
|Délai administratif de soutenance de thèse