PEGylated pH-Responsive Liposomes for Enhancing the Intracellular Uptake and Cytotoxicity of Paclitaxel in MCF-7 Breast Cancer Cells.

Autor: Nijhawan HP; Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS (Deemed to Be University), Mumbai, India., Shyamsundar P; Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS (Deemed to Be University), Mumbai, India., Prabhakar B; Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS (Deemed to Be University), Mumbai, India., Yadav KS; Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS (Deemed to Be University), Mumbai, India. khush.yadav@gmail.com.
Jazyk: angličtina
Zdroj: AAPS PharmSciTech [AAPS PharmSciTech] 2024 Sep 17; Vol. 25 (7), pp. 216. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1208/s12249-024-02930-7
Abstrakt: This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180-200 nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64 nm) and a more negative zeta potential (-36.94 ± 0.32 mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC 50 value of 1.107 µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.
(© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
Databáze: MEDLINE
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