Development and evaluation of coenzyme Q10 loaded solid lipid nanoparticle hydrogel for enhanced dermal delivery

Abstract

Skin is the protective organ of the body with an area around 2 m 2 . The hazardous potential of toxins, pathogens and UV radiation are avoided by the protection that skin supplies (1). UV radiation is the main source of energy that initiates reactive oxygen species (ROS). Formation of ROS leads to oxidative damage in DNA, proteins and lipids. The skin has an enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and non-enzymatic (antioxidant) protection mechanism against these damages; however, excess ROS production overcomes this protection and causes several diseases such as cancer (2, 3). Hence, effective delivery of an antioxidant into skin in required levels is an important challenge. There are two main steps limiting the effective delivery antioxidants, oxidation of the active substance and carrying the active substance to the viable epidermis.Antioxidants are defined as substances that, when present in a low concentration compared to that of oxidizable substrates, significantly delay or inhibit oxidation of that substance (4). In general, antioxidants act by the chain breaking reaction, by reducing the concentration of reactive oxygen species, by scavenging initiating radicals and by chelating transition metal catalysts (5). Coenzyme Q10 (Q10) is the only lipid soluble endogenous antioxidant. It supports ATP generation during aerobic cellular respiration in the electron transport chain in the mitochondria and inhibits cell membrane peroxidation in reduced form (6, 7). However, it is very difficult to prepare a formulation that helps Q10 delivery to deeper layers of the skin due to the low aqueous solubility of Q10 (log P >10) and due to the barrier function of stratum corneum (8).In the second half of the nineties there was an increasing interest in investigating solid lipid nanoparticles (SLNs) for dermal application. SLNs have many advantages, especially for dermal applications such as occlusion, modulation of drug release and penetration into the skin (9). Since they are made from solid lipids, chemically unstable lipid soluble compounds that are sensitive to oxidation can be successfully encapsulated in the SLNs (8, 10). Several molecules were incorporated into lipid nanoparticles, e.g., ascorbyl palmitate, resveratrol, retinol and retinyl palmitate, vitamin E and vitamin E acetate (8,(11)(12)(13)(14). It has been shown that systemic uptake of active substances (e.g., isotretinoin) through skins could be avoided and SLN could increase the accumulative uptake of the active material in the skin (15). SLNs are produced as liquid dispersions and their incorporation into hydrogels or emulsions helps enhance the retention time in the applied area and patient compliance (16,17).Hydrogels are generally formed from carbomers that have the ability to absorb water, get hydrated and swell by neutralization with a base. Carbomers have been mainly used in liquid or semi-solid pharmaceutical formulations in order to modify their flow characteristics (17,18).The aim of this work was to carry an effic...

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“…It is known that the rheology of the formulations can alter the residence time on the eye surface. The increased viscosity values increases residence time on the application area especially in topical formulations (Korkmaz et al, 2013).…”

Preparation of a mixed-matrix hydrogel of vorinostat for topical administration on the rats as experimental model

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EFFECTIVITY AND PHYSICOCHEMICAL STABILITY OF NANOSTRUCTURED LIPID CARRIER COENZYME Q10 IN DIFFERENT RATIO of LIPID ALFA CETYL PALMITATE AND ALPHA TOCOPHERYL ACETATE AS CARRIER

“…The low viscosity effect on the high rate of release of drug substance caused by of constraints (steric barrier) intermolecular loose so that the drug molecule is easier to out. Concentration ratio also affects the pH, PI, and the zeta potential but the value is not equal with the addition of a lipid component [14,18].…”