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Drug Dev Ind Pharm. 2017 Nov;43(11):1792-1800. doi: 10.1080/03639045.2017.1339083. Epub 2017 Jun 21.

Development and characterization of new and scalable topical formulations containing N-acetyl-d-glucosamine-loaded solid lipid nanoparticles.

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a Faculty of Pharmacy, Research Institute for Medicines and Pharmaceutical Sciences (iMed.ULisboa) , Universidade de Lisboa , Lisbao , Portugal.
b Department of Drug Sciences , University of Pavia , Italy.


N-Acetyl-d-glucosamine (NAG) has been recently considered for topical treatment of hyperpigmentation disorders due to its inhibitory effect on thyrosinase enzymes in melanocytes. NAG is a precursor of hyaluronic acid, increasing its amount in skin, and consequently, preserving the skin hydration and elasticity. It may also act as an emulsion stabilizer. Solid lipid nanoparticles (SLN) are advanced delivery systems successfully used in pharmaceutical and cosmetic formulations for the improvement of active molecules penetration into the skin. Therefore, this work aimed to develop and characterize stable and scalable topical formulations containing NAG-loaded SLN. NAG was incorporated in SLN which were prepared by two high shear homogenizers and characterized regarding its morphology and particle size by transmission electron microscopy and photon correlation spectroscopy, respectively. Oil emulgel and hydrogel were used as carriers of NAG-loaded SLN. Several parameters were evaluated, including the droplet size distribution, rheology, pH and topical delivery by different techniques. It was observed that SLN size was significantly dependent on NAG incorporation and homogenization process. Most tested SLN parameters appeared to be quite suitable, that is, spherical and well-defined SLN with approximately 258 nm and -30 mV. Hereafter, both gels containing SLN presented a pseudoplastic flow. Emulgel formulation containing NAG-loaded SLN allowed a higher NAG permeation through the SC compared to the respective control (about 0.8 μgcm-2 h-1). According to the results obtained, it can be suggested that NAG acts as an emulsion stabilizer. This stabilization was also particularly dependent on the homogenizer type which is quite important for scale-up process. This study demonstrated the potential of scalable SLN formulations to improve NAG topical delivery contributing to the improvement of skin properties on several skin disorders.


N-acetyl-d-glucosamine; Solid lipid nanoparticles; emulsion stabilizer effect; homogenization processes; scalable processes; topical gels

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