Nanostructured Lipid Carrier–Based Gel for Repurposing Simvastatin in Localized Treatment of Breast Cancer: Formulation Design, Development, and In Vitro and In Vivo Characterization

Simvastatin (SMV) is noticed as a repurposed candidate to be effective against breast cancer (BC). However, poor solubility, dose-limiting toxicities, and side effects are critical hurdles in its use against BC. The above drawbacks necessitate the site-specific (localized) delivery of SMV via suitable nanocarriers. Therefore, the present study intended to develop SMV nanostructured lipid carrier (NLC)–based gel using carbopol-934 as a gelling agent to achieve local delivery and improve patient compliance while combating BC. The SMV NLCs were fabricated by melt-emulsification ultrasonication technique using stearic acid as solid lipid, olive oil (OO) as liquid lipid, tween 20 as a surfactant, and PEG-200 as a co-surfactant, and optimized by Box-Behnken design. The optimized SMV-loaded NLCs displayed % entrapment efficiency of 91.66 ± 5.2% and particle size of 182 ± 11.9 nm. The pH of NLC-based gels prepared using a 2.0% w/v of carbopol-934 was found in the range of 5.3–5.6 while the viscosity was in the range of 5.1–6.6 Pa.S. Besides, NLC-based gels exhibited higher and controlled SMV release (71–76%) at pH 6.8 and (78–84%) at pH 5.5 after 48 h than SMV conventional gel (37%) at both pH 6.8 and 5.5 after 48 h. The ex vivo permeation of SMV from NLC-based gel was 3.8 to 4.5 times more than conventional gel. Notably, SMV-loaded NLCs displayed ameliorated cytotoxicity than plain SMV against MCF-7 and MDA-MB-231 BC cells. No substantial difference was noticed in the cytotoxicity of NLC-based gels and pure SMV against both cell lines. The SMV NLC-based gel exhibited the absence of skin irritation in vivo in the mice following topical application. In addition, the histopathological study revealed no alteration in the mice skin anatomy. Furthermore, the SMV-loaded NLCs and NLC-based gels were stable for 6 months at refrigerator conditions (4°C ± 2°C). Thus, the present research confirms that NLC-based gel can be a safe, efficacious, and novel alternative to treat BC. Graphical Abstract.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

AAPS PharmSciTech - 24(2023), 5 vom: 21. Apr.

Sprache:

Englisch

Beteiligte Personen:

Kumbhar, Popat S. [VerfasserIn]
Manjappa, Arehalli S. [VerfasserIn]
Shah, Rohit R. [VerfasserIn]
Nadaf, Sameer J. [VerfasserIn]
Disouza, John I. [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

Themen:

Cytotoxicity
Nanostructured lipid carrier–based gel
Permeation
Simvastatin
Skin irritation

Anmerkungen:

© The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1208/s12249-023-02565-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2134610603

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