article · Journal of Drug Delivery Science and Technology
Essential oil extracted from Pistacia lentiscus resins via green hydrodistillation has shown antiproliferative activity against ovarian and breast cancer cells, yet its practical therapeutic use is hindered by volatility, hydrophobicity, and poor bioavailability. To overcome these limitations, the oil was encapsulated into niosomes using a thin-film hydration method. The resulting spherical nanoparticles achieved high entrapment efficiency, remained stable over 21 days of storage, and provided sustained release over 72 hours. Encapsulation improved the cytotoxic potency by ten-fold against Skov-3 ovarian and MCF-7 breast cancer cell lines, while demonstrating a safe profile toward healthy breast epithelial cells. Furthermore, the oil-loaded niosomes induced cell cycle arrest at the sub-G1 phase, increased the expression of pro-apoptotic genes Bak and Bax, and reduced the expression of anti-apoptotic Bcl-2 significantly more effectively than free essential oil.
Natural compounds from plant resins offer promising anti-cancer properties, but physical limitations like rapid evaporation and poor water solubility frequently prevent their medical use. Using nanotechnology to formulate niosomal carriers stabilises these fragile plant extracts and sharply enhances their targeted killing of cancer cells, providing a foundation for safer and more effective plant-based cancer therapies.
This research is in early-stage laboratory development, having been evaluated entirely in vitro on cultured cancer cell lines. It could enable pharmaceutical formulators and drug delivery developers to design targeted nanomedicines utilising plant extracts for breast and ovarian cancer treatments. Substantial progression through in vivo animal models, toxicology profiling, and clinical trials will be necessary before any real-world commercial therapy can be realised.
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The essential oils extracted from Pistacia lentiscus resins possess promising antiproliferative effects against ovarian and breast cancer cells because of their high content of bioactive compounds. However, PO has many drawbacks that hinder its application in breast cancer therapy, such as increased volatility, hydrophobicity, and limited bioavailability. In this study, niosomal formulation loaded with Pistacia lentiscus essential oil (PO) was formulated with improved stability and cytotoxicity against two cancer cell lines. In this regard, PO was extracted from the resins of Chios mastic utilizing a green approach, hydrodistillation. Its chemical composition was analyzed using gas-chromatography–mass spectrometry. PO loaded-niosomes (PO/Ns) were prepared using the thin-film hydration method. The prepared nanovesicles were spherical and had an average size of 230.3 ± 3.7 nm, polydispersity index of 0.13 ± 0.03, and ζ potential (ZP) of −20.36 ± 4.89 mV. PO/Ns had high entrapment efficiency (EE) of 80.59 ± 3.37% and displayed a sustained release manner of PO (83.74 ± 3.34%) over 72 h. Moreover, the developed PO/Ns formulation exhibited outstanding stability in terms of size, PDI, ZP, and EE% when stored for 21 days. SRB assay showed that the IC50 values of PO against ovarian (Skov-3) and breast (MCF-7) cancer cell lines improved from 57.04 to 69.1 μg/mL to 4.88 and 7.38 μg/mL, respectively, when encapsulated in niosomes (PO/Ns). Loading PO in niosomes (PO/Ns) increased its cytotoxicity by 10-folds against Skov-3 and MCF-7 cancer cells. On the other hand, the safety of both PO and PO/Ns was evident by a computed IC50 of >200 μg/mL against the normal breast epithelial cell line (MCF10A). PO/Ns showed enhanced apoptotic effects (combined early and late apoptosis) of 9-fold and 4-fold against Skov-3 and MCF-7 cells, respectively, as compared to unloaded PO treatment. Cell cycle analysis revealed that PO/Ns mainly targets the sub-G1 phase, where it traps the cells, providing further evidence for the induction of apoptosis in both SKOV-3 and MCF-7 cancer cells. Real-time PCR (RT-qPCR) was performed to quantify the gene expression of pro-apoptotic markers as Bak and Bax, as well as the antiapoptotic marker Bcl-2 upon exposure to PO and PO/Ns treatments. Both PO and PO/Ns demonstrated a remarkable ability to upregulate Bak and Bax, and downregulate Bcl-2. As expected, the upregulation of pro-apoptotic genes and induction of mitochondrial death was significantly higher with PO/Ns than pure PO treatment among the two investigated cell lines (Skov-3 and MCF-7). Essential oils extracted from Pistacia lentiscus resins and encapsulated into niosomes showed significant cytotoxic and apoptotic effects against breast and ovarian cancer cells.
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DOI: 10.1016/j.jddst.2023.104820
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