Co-delivery of isotretinoin and clindamycin by phospholipid-based mixed micellar system confers synergistic effect for treatment of acne vulgaris

Abstract

Background

The combination therapy of Isotretinoin (ITR) and antibacterial formulations administered through topical route suffer from several limitations including reduced therapeutic efficacy and low patient-compliance.

Experiment

The present study aimed to develop biocompatible lipid-based mixed micelles of ITR in combination with Clindamycin phosphate (CLIN) employing self-assembly method to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy.

Results

The MTT assay and cellular uptake studies showed non-cytotoxic effect to HaCat cell lines. The zone of inhibition studies conducted in Propionibacterium acnes provides the first literature evidence to support the antimicrobial property of Isotretinoin and Tretinioin. The nano-sized carriers offered (19.3 ± 1.03 nm particle size with −3.12 mV zeta potential) enhanced permeation, skin retention, pre-clinical efficacy and significant skin biocompatibility. The testosterone-induced acne model proved superior pharmacodynamic efficacy of lab developed formulation vis-à-vis marketed products of both the drugs. The results were further confirmed by the histopathological studies of respective skin samples treated with different formulations.

Conclusion

The lab developed lipid-based micellar formulation of ITR and CLIN offers a better strategy for the combined delivery of unstable molecules like ITR and CLIN in acne management.

ABSTRACT

KEYWORDS:

• Propionibacterium acnes
• retinoid
• lipid
• HaCat cells
• combination therapy
• testosterone-induced acne model
• anti-microbial
• stability

Acknowledgments

Authors are thankful to M/s Ipca Laboratories Ltd., Mumbai, for generously providing the gift samples of ITR and CLIN. The authors also express their gratitude to M/s Phospholipid GmbH, Nattermannallee, Germany, for the ex-gratis supply of Phospholipids.

Author contributions

Gajanand Sharma: Conceptualization, Data curation, Methodology, Validation, Visualization, Writing-original draft. Yukhti Yachha: Methodology, Validation, Methodology. Kanika Thakur: Methodology, Investigation, Writing-review & editing. Akanksha Mahajan: Investigation, Methodology. Gurjeet Kaur: Validation, Formal analysis. Bhupinder Singh: Validation, Formal Analysis, Supervision. Kaisar Raza: Validation, Formal analysis, Investigation, Supervision. Om Prakash Katare: Conceptualization, Investigation, Project administration, Supervision, Visualization.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.