AAPS PharmSciTech

, 20:162 | Cite as

Development of MART for the Rapid Production of Nanostructured Lipid Carriers Loaded with All-Trans Retinoic Acid for Dermal Delivery

  • Vivek M. Ghate
  • Arun K. Kodoth
  • S. Raja
  • B. Vishalakshi
  • Shaila A. LewisEmail author
Research Article


All-trans retinoic acid (ATRA) has been regarded as a wonder drug for many dermatological complications; however, its application is limited due to the extreme irritation, and toxicity seen once it has sufficiently concentrated into the bloodstream from the skin. Thus, the present study was aimed to increase the entrapment of ATRA and minimize its transdermal permeation. ATRA incorporated within nanostructured lipid carriers (NLCs) were produced by a green and facile thin lipid-film based microwave-assisted rapid technique (MART). The optimization was carried out using the response surface methodology (RSM)-driven artificial neural network (ANN) coupled with genetic algorithm (GA). The liquid lipid and surfactants were seen to play a very crucial role culminating in the particle size (< 70 nm), zeta potential (< − 32 mV), and entrapment of ATRA (> 98%). ANN-GA-optimized NLCs required a minimal quantity of the surfactants, formed within 2 min and were stable for 1 year at different storage conditions. The optimized NLC-loaded creams showed a skin retention (ex vivo) to an extent of 87.42% with no detectable drug in the receptor fluid (24 h) in comparison to the marketed cream which released 47.32% (12 h) of ATRA. The results were in good correlation with the in vivo skin deposition studies. The NLCs were biocompatible and non-skin irritant based on the primary irritation index. In conclusion, the NLCs were seen to have a very high potential in overcoming the drawbacks of ATRA for dermal delivery and could be produced conveniently by the MART.


all-trans retinoic acid nanostructured lipid carriers artificial neural network stability skin irritation genetic algorithm 



The authors are grateful to the Council of Scientific and Industrial Research (CSIR), New Delhi, for providing financial assistance in the form of Senior Research Fellowship (SRF) to Vivek M. Ghate [File No. 8/602(0003)/18 EMR-1]. The authors are also thankful to Mangalore University, Mangalagangotri, for their support in analyzing the samples.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12249_2019_1307_MOESM1_ESM.docx (8.2 mb)
ESM 1 (DOCX 8406 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Vivek M. Ghate
    • 1
  • Arun K. Kodoth
    • 2
  • S. Raja
    • 3
  • B. Vishalakshi
    • 2
  • Shaila A. Lewis
    • 1
    Email author
  1. 1.Department of Pharmaceutics, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia
  2. 2.Department of Post-Graduate Studies & Research in ChemistryMangalore UniversityMangalagangothri (DK)India
  3. 3.Department of Chemical Engineering, Manipal Institute of TechnologyManipal Academy of Higher EducationManipalIndia

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