Abstract
Objectives: The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC). Methods: Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX. Results: The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs. Conclusions: The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman’s correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.
Highlights
Cancer is one of the most important causes of death worldwide [1]
The antitumor effect was measured in measured in terms tumor mass, necrosis and apoptosis
In the current study the DOXY-PNPs were prepared by nanoprecipitation technique and evaluated for EE% and the loading capacity
Summary
Cancer is one of the most important causes of death worldwide [1] It is characterized by uncontrolled cell proliferation and growth. Ehrlich carcinoma is a mouse breast cancer cell line which is highly similar to the human tumors and acquires high sensitivity to diverse types of antitumor agents [2]. The side effects of DOXY involves inhibition of mitochondrial biogenesis due to the similarity between the mitochondrial ribosomes and bacterial ribosomes [8]. This side effect has been repurposed as a therapeutic option in the field of oncology aiming to inhibit the mitochondrial biogenesis in cancer cells [9]. The adverse effects of DOXY are rare including thrombocytopenia, anemia and neutropenia [10]
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