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.
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).