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Quality by design endorsed atorvastatin-loaded nanostructured lipid carriers embedded in pH-responsive gel for
Deepkumar Bagasariya1, Kondasingh Charankumar1, Saurabh Shah1
1Department of Pharmaceutics, Pharmaceutical Innovation and Translational Research Lab (PITRL), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
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.
