In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery
Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cyt...
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| Format: | Article |
| Language: | English |
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MDPI
2020
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| Online Access: | http://eprints.utm.my/93589/1/NorhayatiMohamedNoor2020_InVitroPerformanceofDutasteride.pdf |
| _version_ | 1796865653625323520 |
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| author | Mohamed Noor, Norhayati Abdul Aziz, Azila Sheikh, Khalid Somavarapu, Satyanarayana Taylor, Kevin M. G. |
| author_facet | Mohamed Noor, Norhayati Abdul Aziz, Azila Sheikh, Khalid Somavarapu, Satyanarayana Taylor, Kevin M. G. |
| author_sort | Mohamed Noor, Norhayati |
| collection | ePrints |
| description | Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (−18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p >0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4–8◦ C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC50 values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride. |
| first_indexed | 2024-03-05T21:00:15Z |
| format | Article |
| id | utm.eprints-93589 |
| institution | Universiti Teknologi Malaysia - ePrints |
| language | English |
| last_indexed | 2024-03-05T21:00:15Z |
| publishDate | 2020 |
| publisher | MDPI |
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| spelling | utm.eprints-935892021-12-31T08:45:33Z http://eprints.utm.my/93589/ In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery Mohamed Noor, Norhayati Abdul Aziz, Azila Sheikh, Khalid Somavarapu, Satyanarayana Taylor, Kevin M. G. Q Science (General) TP Chemical technology Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (−18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p >0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4–8◦ C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC50 values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride. MDPI 2020-10 Article PeerReviewed application/pdf en http://eprints.utm.my/93589/1/NorhayatiMohamedNoor2020_InVitroPerformanceofDutasteride.pdf Mohamed Noor, Norhayati and Abdul Aziz, Azila and Sheikh, Khalid and Somavarapu, Satyanarayana and Taylor, Kevin M. G. (2020) In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery. Pharmaceutics, 12 (10). pp. 1-20. ISSN 1999-4923 http://dx.doi.org/10.3390/pharmaceutics12100994 DOI:10.3390/pharmaceutics12100994 |
| spellingShingle | Q Science (General) TP Chemical technology Mohamed Noor, Norhayati Abdul Aziz, Azila Sheikh, Khalid Somavarapu, Satyanarayana Taylor, Kevin M. G. In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery |
| title | In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery |
| title_full | In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery |
| title_fullStr | In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery |
| title_full_unstemmed | In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery |
| title_short | In vitro performance of dutasteride-nanostructured lipid carriers coated with lauric acid-chitosan oligomer for dermal delivery |
| title_sort | in vitro performance of dutasteride nanostructured lipid carriers coated with lauric acid chitosan oligomer for dermal delivery |
| topic | Q Science (General) TP Chemical technology |
| url | http://eprints.utm.my/93589/1/NorhayatiMohamedNoor2020_InVitroPerformanceofDutasteride.pdf |
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