Ultrasound-assisted efficient targeting of doxorubicin to the tumor microenvironment by lyso-thermosensitive liposomes of varying phase transition temperatures

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2025-01-23 DOI:10.1016/j.ejps.2025.107024
Seyedeh Maryam Hosseinikhah , Leila Farhoudi , Farshad Mirzavi , Fatemeh Vahdat-Lasemi , Leila Arabi , Fatemeh Gheybi , Ameneh Sazgarnia , Seyedeh Hoda Alavizadeh , Mahmoud Reza Jaafari
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Abstract

Premature drug release is the primary hindrance to the effective function of the lyso-thermosensitive liposomes (LTSLs) of doxorubicin (Dox), known as ThermoDox® for the treatment of cancer. Herein, we have optimized LTSLs by using a combination of phospholipids (PLs) with high transition temperatures (Tm) to improve the therapeutic outcome in an assisted ultrasound approach. For this, several Dox LTSLs were prepared using the remote loading method at varying molar ratios (0 to 90 %) of DPPC (Tm 41 °C) and HSPC (Tm 54.5 °C), as well as a constant molar ratio of MSPC (10 %), DSPE-mPEG2000 (4 %). The treatment efficacy was explored by using ultrasound as external hyperthermia (HT) (40–42℃) in mice bearing C26 murine colon carcinoma. All the formulations had an average diameter of around 110 nm, PDI ≤ 0.15, zeta potential of around -12 mV, and Dox encapsulation of >90 %. The cytotoxicity results indicated a higher IC50 value of Dox-LTSLs compared to the ThermoDox® (F0: DPPC:MSPC:DSPE-mPEG2000, 90:10:4), attributed to the faster Dox release in F0 formulation devoid of HSPC. Among various formulations, F25 (DPPC: MSPC: DSPE-mPEG2000: HSPC, 65:10:4:25) showed the highest cellular uptake at 42℃ and significantly improved the antitumor and survival efficacy in mice bearing C26 colon carcinoma in combination with ultrasonic HT compared to F0. Collectively, results demonstrated that optimizing the rigidity of the liposomal bilayers through the combinatorial selection of PLs of different transition temperatures could improve the plasma stability of the liposome, and hence ameliorate the outcome of therapy in assistance with an effective HT approach.

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CiteScore
9.60
自引率
2.20%
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248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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