Formulation and Characterization of Doxycycline-Loaded Polymeric Nanoparticles for Testing Antitumor/Antiangiogenic Action in Experimental Colon Cancer in Mice

Abstract

Nanotherapeutics can enhance the characteristics of drugs, such as rapid systemic clearance and systemic toxicities. Polymeric nanoparticles (PRNPs) depend on dispersion of a drug in an amorphous state in a polymer matrix. PRNPs are capable of delivering drugs and improving their safety. The primary goal of this study is to formulate doxycycline-loaded PRNPs by applying the nanoprecipitation method. Eudragit S100 (ES100) (for DOX-PRNP1) and hydroxypropyl methyl cellulose phthalate HP55 (for DOX-PRNP2) were tested as the drug carrying polymers and the DOX-PRNP2 showed better characteristics and drug release % and was hence selected to be tested in the biological study. Six different experimental groups were formed from sixty male albino mice. 1,2,-Dimethylhydrazine was used for 16 weeks to induce experimental colon cancer. We compared the oral administration of DOX-PRNP2 in doses of 5 and 10 mg/kg with the free drug. Results indicated that DOX-PRNP2 had greater antitumor activity, as evidenced by an improved histopathological picture for colon specimens as well as a decrease in the tumor scores. In addition, when compared to free DOX, the DOX-PRNP2 reduced the angiogenic indicators VEGD and CD31 to a greater extent. Collectively, the findings demonstrated that formulating DOX in PRNPs was useful in enhancing antitumor activity and can be used in other models of cancers to verify their efficacy and compatibility with our study.

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer

“…Therefore, reducing the IFP by normalizing the vasculature is key to enhancing the efficacy of chemotherapy [5]. Some current studies are using nanocarriers to achieve the combined application of antivascular drugs and chemotherapeutic drugs [72,[78][79][80][81][82][83][84]. It has been reported that moderate-dose anti-angiogenic drugs can kill small nonfunctional blood vessels to normalize the tumor vasculature, resulting in increased the accumulation of and penetration by the chemotherapeutic drug and a significant improvement in the oxygen concentration within solid tumors [85].…”

Ultrasonic Transformation of Antibiotic Molecules into a Selective Chemotherapeutic Nanodrug

“…The common treatment for breast cancer involves surgery, radiation therapy, chemotherapy, hormone therapy, and targeted therapy. Recently, novel anticancer agents have been identified among numerous antibiotics [ 6 , 7 , 8 , 9 ]. It has been found that antibiotics (actinomycin, monensin, ivermectin, doxycycline, and salinomycin) could also have synergistic anti-tumor effects by inhibiting anti-apoptotic proteins and proteins involved in angiogenesis and migration of tumor cells [ 8 , 9 , 10 ].…”

“…Nanoparticle-mediated delivery of drugs is a promising approach for cancer treatment that involves the use of nanomaterials to deliver drugs directly to cancer cells while reducing damage to healthy cells. Doxycycline conjugated with or loaded into polymeric, metallic, or liposome nanoparticles has shown considerable antitumor effects on various types of cancer cells [ 7 , 12 , 16 , 17 , 18 ]. Copper nanoparticles conjugated with doxycycline showed excellent antitumor effects on HeLa and HepG2 cells in a synergistic manner [ 18 ].…”

A Validated HPLC Multichannel DAD Method for the Simultaneous Determination of Amoxicillin and Doxycycline in Pharmaceutical Formulations and Wastewater Samples

“…Dox is a broad-spectrum antibiotic belonging to the tetracycline class, usually used in the management and treatment of various infections caused by Gram-positive and Gram-negative bacteria, rickettsiae, chlamydiae, spirochetes, mycoplasmas, and protozoans [23,24]. Compared with other tetracyclines, doxycycline has a better absorption profile, longer half-life, safety profile, and excellent efficacity for susceptible microorganisms, even at lower concentrations [25,26].…”

“…Compared with other tetracyclines, doxycycline has a better absorption profile, longer half-life, safety profile, and excellent efficacity for susceptible microorganisms, even at lower concentrations [25,26]. Doxycycline monohydrate and doxycycline hyclate are equally effective, but doxycycline hyclate is more frequently uwatersed in pharmaceutical samples due to its good water solubility [24]. Amoxicillin (Amox) Doxycycline (Dox)…”