Quality by design endorsed atorvastatin-loaded nanostructured lipid carriers embedded in pH-responsive gel for melanoma

Abstract

Aim

Our aim was to repurpose atorvastatin for melanoma by encapsulating in a nanostructured lipid carrier matrix to promote tumour cell internalisation and skin permeation. pH-responsive chitosan gel was employed to restrict At-NLCs in upper dermal layers.

Methods

We utilised a quality by design approach for encapsulating At within the NLC matrix. Further, cellular uptake and cytotoxicity was evaluated along with pH-responsive release and ex vivo skin permeation.

Results

Cytotoxicity assay showed 3.13-fold enhanced cytotoxicity on melanoma cells compared to plain drug with nuclear staining showing apoptotic markers. In vitro, release studies showed 5.9-fold rapid release in chitosan gel matrix at pH 5.5 compared to neutral pH.

Conclusions

At-NLCs prevented precipitation, promoted skin permeation, and SK-MEL 28 cell internalisation. The localisation of NLCs on the upper dermal layer due to electrostatic interactions of skin with chitosan gel diminished the incidence of untoward systemic effects.

Keywords:

• Melanoma
• nanostructured lipid carriers
• atorvastatin
• pH-responsive gel

Acknowledgement

The authors would like to acknowledge the research funding support by the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Govt. of India to “Pharmaceutical Innovation and Translational Research Lab (PITRL),” Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad, INDIA.

Credit author statement

Deepkumar Bagasariya, Kondasingh Charankumar – Conceptualisation, data curation, original draft writing and editing; Saurabh Shah, Paras Famta – Data curation, original draft editing; Valencia Fernandes – Data curation; Syed Shahrukh - Data curation; Dharmendra Kumar Khatri – Supervision and resources; Shashi Bala Singh – Supervision and Saurabh Srivastava – Supervision, resources and validation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.