Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism

Objective: The aim of the present study was to design nanocarriers for the topical application of rivastigmine. Methods: The effect of cosurfactants, hydrophilic gel and loading amount on the permeability of rivastigmine through rat skin was evaluated. Skin irritation tests and stability tests were performed to evaluate the utility of tested formulations. Results: The results showed that the microemulsion formation and characteristics of drug-loaded formulations were related to many parameters of the components. When using microemulsion systems as a vehicle, the permeation rate remarkably increased about 13.2~24.3-fold and the lag time was significantly shortened from 24 h to 4.7 h. Formulations containing a cosurfactant of Diethylene Glycol Monobutyl Ether (DEGBE) showed higher enhancement effect, while increasing the loading dose from 0.5% to 5% further increased the flux about 2.1-fold and shortened the lag time. Conclusion: The drug-loaded experimental formulation did not cause skin irritation and had good stability at 20ºC and 40ºC storage for at least 3 months. The result showed that gel-based microemulsion formulation could be a promising approach for topical administration.

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The topical administration of rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) improves healing in a porcine full-thickness excisional wound model

Journal of Controlled Release ◽

10.1016/j.jconrel.2014.10.033 ◽

2015 ◽

Vol 197 ◽

pp. 41-47 ◽

Cited By ~ 52

Author(s):

Garazi Gainza ◽

Diego Celdran Bonafonte ◽

Beatriz Moreno ◽

José Javier Aguirre ◽

Francisco Borja Gutierrez ◽

...

Keyword(s):

Topical Administration ◽

Nanostructured Lipid Carriers ◽

Full Thickness ◽

Wound Model ◽

Excisional Wound

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In Vitro Performance of Dutasteride-Nanostructured Lipid Carriers Coated with Lauric Acid-Chitosan Oligomer for Dermal Delivery

Pharmaceutics ◽

10.3390/pharmaceutics12100994 ◽

2020 ◽

Vol 12 (10) ◽

pp. 994

Author(s):

Norhayati Mohamed Noor ◽

Azila Abdul-Aziz ◽

Khalid Sheikh ◽

Satyanarayana Somavarapu ◽

Kevin M. G. Taylor

Keyword(s):

Lauric Acid ◽

Skin Irritation ◽

Systemic Exposure ◽

Entrapment Efficiency ◽

Nanostructured Lipid Carriers ◽

Androgenic Alopecia ◽

Fluorescent Marker ◽

Chitosan Oligomer ◽

Coumarin 6

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.

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