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

被引:5
|
作者
Bagasariya, Deepkumar [1 ]
Charankumar, Kondasingh [1 ]
Shah, Saurabh [1 ]
Famta, Paras [1 ]
Fernandes, Valencia [2 ]
Shahrukh, Syed [1 ]
Khatri, Dharmendra Kumar [2 ]
Singh, Shashi Bala [2 ]
Srivastava, Saurabh [1 ,3 ]
机构
[1] Natl Inst Pharmaceut Educ & Res NIPER, Dept Pharmaceut, Pharmaceut Innovat & Translat Res Lab PITRL, Hyderabad, India
[2] Natl Inst Pharmaceut Educ & Res NIPER, Dept Biol Sci, Hyderabad, India
[3] Natl Inst Pharmaceut Educ & Res NIPER, Dept Pharmaceut, Pharmaceut Innovat & Translat Res Lab PITRL, Hyderabad 500037, India
关键词
Melanoma; nanostructured lipid carriers; atorvastatin; pH-responsive gel; DELIVERY; CANCER; NANOPARTICLES; OPTIMIZATION; PRENYLATION; MECHANISM; APOPTOSIS; HYDROGEL; STATINS; PROFILE;
D O I
10.1080/02652048.2023.2282971
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
AimOur 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.MethodsWe 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.ResultsCytotoxicity 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.ConclusionsAt-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.
引用
收藏
页码:27 / 44
页数:18
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