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Formulation And Evaluation Of Nanostructured Lipid Carriers (NLCs) Of 20(S)-Protopanaxadiol (PPD) By Box-Behnken Design

Authors Kim MH, Kim KT, Sohn SY, Lee JY, Lee CH, Yang H, Lee BK, Lee KW, Kim DD

Received 15 May 2019

Accepted for publication 24 September 2019

Published 25 October 2019 Volume 2019:14 Pages 8509—8520

DOI https://doi.org/10.2147/IJN.S215835

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J. Webster


Min-Hwan Kim,1 Ki-Taek Kim,2 Seo-Yeon Sohn,1 Jae-Young Lee,3 Chang Hyung Lee,4 Hee Yang,4 Bo Kyung Lee,5 Ki Won Lee,4,5 Dae-Duk Kim1

1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, Republic of Korea; 3College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 4Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea; 5Research & Development Center, BOBSNU Co., Ltd., Suwon, Gyeonggi-Do 16229, Republic of Korea

Correspondence: Dae-Duk Kim
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
Tel +82 2 880 7870
Fax +82 2 873 9177
Email ddkim@snu.ac.kr

Background: 20(S)-Protopanaxadiol (PPD) has a higher anti-wrinkle effect than the other glycone forms of ginsenosides. However, as PPD has low solubility in water and a high molecular weight, it cannot easily penetrate the stratum corneum layer, which is the rate-limiting step of topical skin delivery. Thus, the objective was to enhance the topical skin deposition of PPD using an optimized nanostructured lipid carriers (NLC) formulation. NLC formulations were optimized using a Box-Behnken design.
Materials and methods: NLC formulations were optimized using a Box-Behnken design, where the amount of PDD (X1), volume of the liquid lipid (X2), and amount of surfactant (X3) were set as the independent variables, while the particle size (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (EE) (Y3) were dependent factors. An in vitro deposition study was performed using Strat-M® and human cadaver skin, while in vivo skin irritation effect of the NLC formulation was evaluated in humans.
Results: An NLC was successfully prepared based on the optimized formulation determined using the Box-Behnken design. The particle size, PDI, and EE of the NLC showed less than 5% difference from the predicted values. The in vitro deposition of PPD after the application of the NLC formulation on a Strat-M® artificial membrane and human cadaver skin was significantly higher than that of the controls. Moreover, NLC formulations with and without PDD were not skin irritants in a human study.
Conclusion: An NLC formulation for the topical delivery of PPD was successfully optimized using the Box-Behnken design, and could be further developed to enhance the topical skin deposition of PPD.

Keywords: Box-Behnken design, 20(S)-Protopanaxadiol, nanostructured lipid carrier; NLC, Strat-M™, topical delivery

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