Abstract
Encapsulation of the chemotherapy agents within colloidal systems usually improves drug efficiency and decreases its toxicity. In this study, lignin (LGN) (the second most abundant biopolymer next to cellulose on earth) was employed to prepare novel doxorubicin (DOX)-loaded oil-in-water (O/W) microemulsions with the aim of enhancing the bioavailability of DOX. The droplet size of DOX-loaded microemulsion was obtained as ≈ 7.5 nm by dynamic light scattering (DLS) analysis. The entrapment efficiency (EE) % of LGN/DOX microemulsions was calculated to be about 82%. In addition, a slow and sustainable release rate of DOX (68%) was observed after 24 h for these microemulsions. The cytotoxic effects of standard DOX and LGN/DOX microemulsions on non-malignant (HUVEC) and malignant (MCF7 and C152) cell lines were assessed by application of a tetrazolium (MTT) colorimetric assay. Disruption of cell membrane integrity was investigated by measuring intracellular lactate dehydrogenase (LDH) leakage. In vitro experiments showed that LGN/DOX microemulsions induced noticeable morphological alterations and a greater cell-killing effect than standard DOX. Moreover, LGN/DOX microemulsions significantly disrupted the membrane integrity of C152 cells. These results demonstrate that encapsulation and slow release of DOX improved the cytotoxic efficacy of this anthracycline agent against cancer cells but did not improve its safety towards normal human cells. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of microemulsions as a promising drug carrier for overcoming pharmacokinetic limitations.
Highlights
The PDI obtained from dynamic light scattering (DLS) analysis showed values (0.1–0.2), indicating a good size distribution of the oil droplet in the microemulsion system
LGN/DOX microemulsions induced more toxicity in C152 cells compared with standard DOX. This might explain the significant enhancement in lactate dehydrogenase (LDH) leakage in C152 cells exposed to this formulation. These findings suggest that LGN/DOX microemulsions might induce cell death through activation of both apoptosis and necrosis mechanisms
Our results indicated that novel synthesized LGN/DOX microemulsions exert cytotoxic effects on oral and breast carcinoma cells while inducing unfavorable toxic effects on normal human cells
Summary
DOX is slightly soluble in normal saline and sparingly soluble in alcohol, and has broad-spectrum activity against neoplasms, lymphomas, solid tumors, and breast tumors [2]. It has been widely used as a first-line therapy in testicular, breast, and hepatocellular carcinoma. DOX has different biomedical applications in various chemotherapeutic regimens It was previously applied in combination with bleomycin, dacarbazine, cyclophosphamide vincristine, and prednisone for the treatment of non-Hodgkin’s and Hodgkin’s lymphomas. Another application of DOX and cyclophosphamide can be used as adjuvant therapy with or without including fluorouracil followed by paclitaxel for breast cancer. The combination of DOX with a greater dose of cisplatin and methotrexate has been successfully applied to treat osteogenic sarcoma [3,4]
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