Skip to main content

Advertisement

SpringerLink
Log in

Efficacy assessments of tretinoin-loaded nano lipid carriers in acne vulgaris: a double blind, split-face randomized clinical study

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Here, we assessed the efficacy and safety of Nano lipid carrier (NLC) drug delivery system containing tretinoin (NLC-TRE) in comparison with the conventional 0.05% tretinoin cream (TRE cream) in mild to moderate acne vulgaris. A stable and appropriate NLC-TRE formulation was prepared using a high-pressure homogenizer and particle characterization and physicochemical properties were evaluated under accelerated conditions. Efficacy assessment was performed via a split-face clinical study, by comparing the number of acne lesions, porphyrin production and skin biophysical parameters in both sides of the face randomly treated with NLC-TRE and TRE cream. Plasma concentration of tretinoin after topical application of NLC-TRE was measured for primary safety evaluation. We acquired a stable, spherical nanoparticles with particle size of 118.5 nm, PI equal to 0.485 and ZP of − 44.7 mV. The rate of decrease of acne lesions was significantly higher in NLC- TRE side (p value < 0.001). The size and intensity of porphyrin production in pilosebaceous follicles were significantly reduced only on NLC-TRE side (p value < 0.01). The plasma concentration of the tretinoin, after 8 weeks’ application remained lower than the toxic levels. The NLC-TRE formula provides better efficiency and good loading capacity of TRE in the drug delivery system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Zouboulis CC, Abdel-Naser MB (2010) Acne and its variants. In: Krieg T, Bickers D, Miyacki Y (eds) Therapy of skin diseases. Springer, Berlin, pp 359–373

    Chapter  Google Scholar 

  2. Eady EA, Cove JH (2000) Is acne an infection of blocked pilosebaceous follicles? Implications for antimicrobial treatment. Am J Clin Dermatol 1(4):201–209

    Article  CAS  Google Scholar 

  3. Rathi S (2011) Acne vulgaris treatment: the current scenario. Indian J Dermatol 56(1):7–13

    Article  Google Scholar 

  4. Bagatin E, Florez-White M, Arias-Gomez MI et al (2017) Algorithm for acne treatment: Ibero-Latin American consensus. An Bras Dermatol 92(5):689–693

    Article  Google Scholar 

  5. McDaniel DH, Mazur C, Wortzman MS et al (2017) Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol cream or 0.025% tretinoin cream in subjects with mild to severe photoaging. J Cosmet Dermatol 16(4):542–548

    Article  Google Scholar 

  6. Abdel-Naser MB, Zouboulis CC (2008) Clindamycin phosphate / tretinoin gel formulation in the treatment of acne vulgaris. Expert Opin Pharmacother 9:2931–2937

    Article  CAS  Google Scholar 

  7. Thielitz A, Abdel-Naser MB, Fluhr JW et al (2010) Topical retinoids in acne–an evidence-based overview. J Dtsch Dermatol Ges 1:S15-23

    Article  Google Scholar 

  8. Tabbakhian M, Sharifian A (2008) Preparation and in vitro characterization of tretinoin-containing. Res Pharmaceut Sci 3(2):31–40

    Google Scholar 

  9. Duclairoir C, Orecchioni AM, Depraetere P et al (2003) Evaluation of gliadins nanoparticles as drug delivery systems: a study of three different drugs. Int J Pharm 253(1–2):133–144

    Article  CAS  Google Scholar 

  10. Amdidouche D, Montassier P, Poelman MC et al (1994) Evaluation by laser Doppler velocimetry of the attenuation of tretinoin induced skin irritation by β-cyclodextrin complexation. Int J Pharmaceut 1994:111–116

    Article  Google Scholar 

  11. Naseri N, Valizadeh H, Zakeri-Milani P (2015) Solid lipid nanoparticles and nanostructured lipid carriers: structure. Prep Appl Adv Pharm Bull 5(3):305–313

    Article  CAS  Google Scholar 

  12. Falcocchio S, Ruiz C, Javier PFI et al (2006) Propionibacterium acnes GehA lipase, an enzyme involved in acne development, can be successfully inhibited by defined natural substances. J Mol Catal B: Enzym 2006:132–137

    Article  Google Scholar 

  13. Raza K, Singh B, Lohan S et al (2013) Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic. Int J Pharm 456(1):65–72

    Article  CAS  Google Scholar 

  14. Sanad R (2014) Lipid nanoparticles (SLNs and NLCs): wide range of application. J Drug Res Egypt 35(1):73–79

    Google Scholar 

  15. Dubey A, Prabhu P, Kamath J (2012) Nano structured lipid carriers: a novel. Int J PharmTech Res 4(2):705–714

    CAS  Google Scholar 

  16. Nasrollahi SA, Hassanzade H, Moradi A et al (2017) Safety assessment of tretinoin loaded nano emulsion and nanostructured lipid carriers: a non-invasive trial on human volunteers. Curr Drug Deliv 14:575–580

    Article  CAS  Google Scholar 

  17. Gasco MR (2007) Lipid nanoparticles: perspectives and challenges. Adv Drug Deliv Rev 59(6):377–378

    Article  CAS  Google Scholar 

  18. Sabouri M, Samadi A, Ahmad Nasrollahi S et al (2018) Tretinoin loaded nanoemulsion for acne vulgaris: fabrication, physicochemical and clinical efficacy assessments. Skin Pharmacol Physiol 31(6):316–323

    Article  CAS  Google Scholar 

  19. Moradi A, Farboud ES, Ahmad-Nasrollahi S et al (2017) Tretinoin Loaded nanostructured lipid carrier (NLC): safe and effective drug delivery system. Nanosci Nanotechnol Asia 2017:221–229

    Google Scholar 

  20. Nastiti CM, Ponto T, Abd E et al (2017) Topical nano and microemulsions for skin delivery. Pharmaceutics 9:37

    Article  Google Scholar 

  21. Weyenberg W, Filev P, Van den Plas D et al (2007) Cytotoxicity of submicron emulsions and solid lipid nanoparticles for dermal application. Int J Pharm 337(1–2):291–298

    Article  CAS  Google Scholar 

  22. Latter G, Grice JE, Mohammed Y et al (2019) Targeted topical delivery of retinoids in the management of acne vulgaris: current formulations and novel delivery systems. Pharmaceutics 24(11):10

    Google Scholar 

  23. Gordillo-Galeano A, Mora-Huertas CE (2018) Solid lipid nanoparticles and nanostructured lipid carriers: a review emphasizing on particle structure and drug release. Eur J Pharm Biopharm 133:285–308

    Article  CAS  Google Scholar 

  24. Shegokar R, Singh KK, Müller RH (2011) Production & stability of stavudine solid lipid nanoparticles—from lab to industrial scale. Int J Pharm 416(2):461–470

    Article  CAS  Google Scholar 

  25. Khurana S, Bedi P, Jain N (2013) Preparation and evaluation of solid lipid nanoparticles based nanogel for dermal delivery of meloxicam. Chem Phys Lipids 175:65–72

    Article  Google Scholar 

  26. Tamjidi F, Shahedi M, Varshosaz J et al (2013) Nanostructured lipid carriers (NLC): a potential delivery system for bioactive food molecules. Innov Food Sci Emerg Technol 19:29–43

    Article  CAS  Google Scholar 

  27. Kovačević AB, Muller RH, Savić SD et al (2014) Solid lipid nanoparticles (SLN) stabilized with polyhydroxy surfactants: preparation, characterization and physical stability investigation. Colloids Surf A Physicochem Eng Asp 444:15–25

    Article  Google Scholar 

  28. Rahman SA, Abdelmalak NS, Badawi A et al (2016) Tretinoin-loaded liposomal formulations: from lab to comparative clinical study in acne patients. Drug Deliv 23(4):1184–1193

    Article  Google Scholar 

  29. Selvamuthukumar S, Velmurugan R (2012) Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy. Lipids Health Dis 11:159

    Article  CAS  Google Scholar 

  30. Almousallam M, Moia C, Huijun Z (2015) Development of nanostructured lipid carrier for dacarbazine delivery. Int Nano Lett 5:241–248

    Article  CAS  Google Scholar 

  31. Manconi M, Sinico C, Valenti D et al (2006) Niosomes as carriers for tretinoin: III. A study into the in vitro cutaneous delivery of vesicle-incorporated tretinoin. Int J Pharm 311:11–19

    Article  CAS  Google Scholar 

  32. Sinico C, Manconi M, Peppi M et al (2005) Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle–skin interaction. J Control Release 103:123–136

    Article  CAS  Google Scholar 

  33. Sanad NS, Tabdelmalak TS, Elbayoomy A (2010) Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs). AAPS PharmSciTech 11:1684–1694

    Article  CAS  Google Scholar 

  34. Dan N (2016) Compound release from nanostructured lipid carriers (NLCs). J Food Eng 171:37–43

    Article  CAS  Google Scholar 

  35. Ghate VM, Lewis SA, Prabhu P et al (2016) Nanostructured lipid carriers for the topical delivery of tretinoin. Eur J Pharm Biopharm 108:253–261

    Article  CAS  Google Scholar 

  36. Adamson PC, Bailey J, Pluda J et al (1995) Pharmacokinetics of all- trans-retinoic acid administered on an intermittent schedule. J Clin Oncol 13:1238–1240

    Article  CAS  Google Scholar 

  37. Lynn K, Joel L, Judy L et al (2003) Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products. JAAD 48(5):740–751

    Article  Google Scholar 

Download references

Funding

No funding source to declare.

Author information

Author notes

  1. Aniseh Samadi and Zohre sartipi contributed equally to this work.

Authors and Affiliations

  1. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, No. 415 Taleqani Ave, Tehran, Iran

    Aniseh Samadi, Zohre Sartipi, Saman Ahmad Nasrollahi, Mansour Nassiri Kashani & Alireza Firooz

  2. Graduate School of Health, University of Technology Sydney, Sydney, Australia

    Behjat Sheikholeslami

  3. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza Rouini & Rassoul Dinarvand

Authors
  1. Aniseh Samadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zohre Sartipi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saman Ahmad Nasrollahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Behjat Sheikholeslami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mansour Nassiri Kashani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mohammad Reza Rouini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rassoul Dinarvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alireza Firooz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of experiments: SAN, AS, AF, RD. Acquisition of data: AS, ZS, BS. Analysis of data: AS. Interpretation of data: AS, SAN. Drafting the work: AS, ZS, BS. Revising the work: SAN, AF, MNK, MRR.

Corresponding author

Correspondence to Saman Ahmad Nasrollahi.

Ethics declarations

Conflicts of interest

The authors have no conflicts of interest to declare.

Statement of Ethics

This study was approved by the Ethics Committee of Tehran University of Medical Sciences under the registration code IR.TUMS.REC.1394.1771. The study protocol was approved by the Committee of Iranian Registry of Clinical Trials on 3/1/2016 under the registration code IRCT20161207031288N2. Data were generated, recorded and processed in accordance with the Declaration of Helsinki and principles of Good Clinical Practice. The method of study was explained to all volunteers, and a written informed consent was obtained.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Samadi, A., Sartipi, Z., Ahmad Nasrollahi, S. et al. Efficacy assessments of tretinoin-loaded nano lipid carriers in acne vulgaris: a double blind, split-face randomized clinical study. Arch Dermatol Res 314, 553–561 (2022). https://doi.org/10.1007/s00403-021-02256-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-021-02256-5

Keywords

Search

Navigation