Mohamed Noor, Norhayati; (2017) Lipid-based Nanoparticles for Topical Delivery of Hair Growth Therapeutic Molecules. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

INTRODUCTION: Androgenic alopecia (AA) patients usually have high levels of dihydrotestosterone on their balding scalp area. Currently, dutasteride (DST) is given orally and has systemic adverse effects; diminished sexual desire, increased depression and ejaculation disorder. Topical administration of DST is an appropriate drug-delivery strategy with the potential to reduce systemic side effect, skin irritation and cytotoxicity effects. MATERIALS AND METHOD: Chitosan oligomer (CSO) conjugated with stearic acid (SA) or lauric acid (LA) was synthesised and characterised. Dutasteride-loaded nanostructured lipid carriers (DST-NLCs) were prepared using a melt-dispersion ultrasonication method. DST-NLCs were optimised using a design of experiments approach. DST-NLCs, uncoated and coated with CSO-SA or CSO-LA were characterised for particle size distribution, surface charge and morphology. In vitro release and permeation studies were performed. Cytotoxicity was investigated using human hair follicle dermal papilla cells, and skin irritation was performed using an EpiDerm™ RHE model. Cou-6 loaded NLCs were prepared and characterised before proceeding with the cell and skin uptake study. RESULTS: CSO-SA and CSO-LA were successfully synthesised; confirmed using 1H NMR and FTIR. The mean size of DST-NLCs was significantly increased (p<0.05) when coated with 5% CSO-SA but not with 5% CSO-LA (p>0.05). The zeta potential changed from negative to positive charge when coating DST-NLCs with CSO-SA or CSO-LA. All formulations were physically stable over six months when stored at 4-8°C. However, DST-NLCs coated with CSO showed aggregation. All formulations exhibited rapid drug release. No dutasteride permeated through pig ear skin after 48 h for all formulations. The cytotoxicity (IC50) for DST nanoparticles, coated and uncoated, was greater than for DST alone (p<0.05). The in vitro skin irritation study indicated no irritation for all nanoparticle preparations. For the cell and skin uptake studies, all samples showed time-dependent skin and cell uptake. CONCLUSIONS: These stable, low cytotoxic and irritant, positively-charged DST-NLCs with CSO-SA or CSO-LA, represents a promising strategy for topical/ transfollicular delivery of DST.

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