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Preformulation and characterization of raloxifene-loaded lipid nanoparticles for transdermal administration

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Abstract

Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24 h, respectively) compared with the unloaded drug (> 90% at 24 h). Unloaded RLX did not permeate the diffusion cells’ receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery.

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Acknowledgements

The authors acknowledge the Chemical Industry of Goiás State (IQUEGO) to provide the necessary facilities and Dr. Luis Antonio Dantas Silva to contribute to DSC measurements.

Funding

This work was supported by Brazilian agencies CNPq, CAPES, and FAPEG.

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Authors and Affiliations

  1. Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Universidade Federal de Goiás (UFG), Rua 240, Setor Leste Universitário, Goiânia, GO, 74.605-170, Brazil

    Guilherme L. Alves, Fernanda V. Teixeira, Priscila Bianca Rodrigues da Rocha, Anna Paula Krawczyk-Santos, Lígia Marquez Andrade, Ricardo N. Marreto & Stephânia F. Taveira

  2. Laboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, University of Brasília, Brasília, DF, Brazil

    Marcilio Cunha-Filho

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  1. Guilherme L. Alves
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  2. Fernanda V. Teixeira
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  3. Priscila Bianca Rodrigues da Rocha
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  4. Anna Paula Krawczyk-Santos
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  5. Lígia Marquez Andrade
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  7. Ricardo N. Marreto
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  8. Stephânia F. Taveira
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Contributions

All the authors have read and approved the manuscript. The study concept was performed by Taveira, S. F. as the study design. Alves, G. L., Teixeira, F. V., Da Rocha, P. B. R., Krawczyk-Santos, A. P., and Andrade, L. M. had performed the data acquisition. Andrade, L. M. and Krawczyk-Santos, A. P had performed quality control of data. Cunha-Filho M., Marreto, R. N., and Taveira, S. F. had carried out data analysis and interpretation. Alves, G. L. had performed the statistical analysis. Taveira, S. F., Cunha-Filho M., and Marreto, R. N. had written and edited the manuscript for intellectual content. All the authors were agreed to be accountable for all aspects of work, ensuring integrity and accuracy.

Corresponding author

Correspondence to Stephânia F. Taveira.

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Experimental procedures were performed according to ethical standards, especially as Normative Resolutions of the National Council for the Control of Animal Experimentation—CONCEA. Approval in June of 2017 by the Ethics Committee on the Use of Animals/CEUA-PRPI-UFG (process number 053/17). The consent to participate does not apply to this study.

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Alves, G.L., Teixeira, F.V., da Rocha, P.B.R. et al. Preformulation and characterization of raloxifene-loaded lipid nanoparticles for transdermal administration. Drug Deliv. and Transl. Res. 12, 526–537 (2022). https://doi.org/10.1007/s13346-021-00949-y

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