Development of MART for the Rapid Production of Nanostructured Lipid Carriers Loaded with All-Trans Retinoic Acid for Dermal Delivery
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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.
KEY WORDSall-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.
- 3.Courant T, Bayon E, Reynaud-Dougier HL, Villiers C, Menneteau M, Marche PN, et al. Tailoring nanostructured lipid carriers for the delivery of protein antigens: physicochemical properties versus immunogenicity studies. Biomaterials. 2017;136:29–42. https://doi.org/10.1016/j.biomaterials.2017.05.001.CrossRefPubMedGoogle Scholar
- 6.Beg S, Saini S, Bandopadhyay S, Katare OP, Singh B. QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of olmesartan medoxomil employing multivariate statistical techniques. Drug Dev Ind Pharm. 2018;44(3):407–20. https://doi.org/10.1080/03639045.2017.1395459.CrossRefPubMedGoogle Scholar
- 8.Kasongo KW, Müller RH, Walker RB. The use of hot and cold high pressure homogenization to enhance the loading capacity and encapsulation efficiency of nanostructured lipid carriers for the hydrophilic antiretroviral drug, didanosine for potential administration to paediatric patients. Pharm Dev Technol. 2012;17(3):353–62. https://doi.org/10.3109/10837450.2010.542163.CrossRefPubMedGoogle Scholar
- 15.Vakilinezhad MA, Tanha S, Montaseri H, Dinarvand R, Azadi A, Akbari Javar H. Application of response surface method for preparation, optimization, and characterization of nicotinamide loaded solid lipid nanoparticles. Adv Pharm Bull. 2018;8(2):245–56. https://doi.org/10.15171/apb.2018.029.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Samson S, Basri M, Fard Masoumi HR, Abdul Malek E, Abedi Karjiban R. An artificial neural network based analysis of factors controlling particle size in a virgin coconut oil-based nanoemulsion system containing copper peptide. Mukherjee A, editor. PLoS One. 2016;11(7):e0157737. https://doi.org/10.1371/journal.pone.0157737.CrossRefGoogle Scholar
- 26.Raza K, Singh B, Lohan S, Sharma G, Negi P, Yachha Y, et al. Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity. Int J Pharm. 2013;456(1):65–72. https://doi.org/10.1016/j.ijpharm.2013.08.019.CrossRefPubMedGoogle Scholar
- 28.Rahman SA, Abdelmalak NS, Badawi A, Elbayoumy T, Sabry N, Ramly A El. Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in-vitro characterization, skin irritation test and comparative clinical study. Drug Deliv 2015;22(6):731–739. https://doi.org/10.3109/10717544.2014.896428.CrossRefGoogle Scholar
- 29.Shetty PK, Venuvanka V, Jagani HV, Chethan GH, Ligade VS, Musmade PB, et al. Development and evaluation of sunscreen creams containing morin-encapsulated nanoparticles for enhanced UV radiation protection and antioxidant activity. Int J Nanomedicine. 2015;10:6477–91. https://doi.org/10.2147/IJN.S90964.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Kodoth AK, Ghate VM, Lewis SA, Badalamoole V. Application of pectin-zinc oxide hybrid nanocomposite in the delivery of a hydrophilic drug and a study of its isotherm, kinetics and release mechanism. Int J Biol Macromol. 2018;115:418–30. https://doi.org/10.1016/j.ijbiomac.2018.04.069.CrossRefPubMedGoogle Scholar
- 39.Chen Y, Zhou L, Yuan L, Zhang Z, Liu X, Wu Q. Formulation, characterization, and evaluation of in vitro skin permeation and in vivo pharmacodynamics of surface-charged tripterine-loaded nanostructured lipid carriers. Int J Nanomedicine. 2012;7:3023–32. https://doi.org/10.2147/IJN.S32476.CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Banerjee S, Chattopadhyay P, Ghosh A, Pathak MP, Singh S, Veer V. Acute dermal irritation, sensitization, and acute toxicity studies of a transdermal patch for prophylaxis against (±) anatoxin-A poisoning. Int J Toxicol. 2013;32(4):308–13. https://doi.org/10.1177/1091581813489996.CrossRefPubMedGoogle Scholar
- 45.Li Y, Abbaspour MR, Grootendorst PV, Rauth AM, Wu XY. Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology. Eur J Pharm Biopharm. 2015;94:170–9. https://doi.org/10.1016/J.EJPB.2015.04.028.CrossRefPubMedGoogle Scholar
- 51.Bos JD, Meinardi MMHM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–9. https://doi.org/10.1034/j.1600-0625.2000.009003165.x.CrossRefPubMedGoogle Scholar