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The obtained results clearly demonstrated that the developed PAADC-DP MMs system is a promising approach for cancer chemotherapy with reduced toxicity.

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Background: Methotrexate (MTX), a folate anti-metabolite, has been used widely in the treatment of plenty of malignancies. However, the clinical use is limited because of its poor water solubility (BCS class II drug), nonspecific distribution, drug resistance, short circulation half-life, and toxicity. The objective of the present research was to synthesize the ester prodrug of MTX with D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and characterize for in vitro anticancer efficacy. Results: The FTIR and NMR results revealed the successful synthesis of the prodrug. The assay and saturation solubility of the prodrug is found to be 23 ± 2.5% and 6.7 ± 1.3 mg/mL (MTX equivalent) respectively. The CMC of the prodrug in distilled water at room temperature is found to be 36.9 ± 2.6 μg/mL. The prepared prodrug micelles showed a mean particle size of 166 ± 10 nm (PDI, 0.325 ± 0.09). Further, the TEM results confirmed the self-assembling character of the prodrug into micelles with a nearly spherical shape. The prodrug caused the significantly (p < 0.01) less hemolysis (16.8 ± 1.5%) when compared to plain MTX solution and significantly higher (p < 0.01) in vitro cytotoxicity, cell cycle arresting, and apoptosis against human breast cancer cells (MCF-7 and MDA-MB-231). Conclusion: Our study results revealed the remarkable in vitro anticancer activity of MTX following its esterification with TPGS. However, further, in vivo studies are needed to prove its efficacy against different cancers.

Background Podophyllotoxin (PPT) is a naturally occurring compound obtained from the roots of Podophyllum species, indicated for a variety of malignant tumors such as breast, lung, and liver tumors. This toxic polyphenol (PPT) exhibited significant activity against P-glycoprotein (P-gp) mediated multidrug-resistant (MDR) cancer cells. However, extremely poor water solubility, a narrow therapeutic window, and high toxicity have greatly restricted the clinical uses of PPT. Therefore, the present research was aimed to synthesize the water-soluble ester prodrug of PPT with polyacrylic acid (PAA), a water-soluble polymer by Steglich esterification reaction, and to screen it for assay, solubility, in vitro hemolysis, in vitro release, and in vitro anticancer activity. Results The Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy results revealed the successful synthesis of podophyllotoxin-polyacrylic acid conjugate (PPC). The assay and saturation solubility of the prodrug is found to be 64.01 ± 4.5% and 1.39 ± 0.05 mg/mL (PPT equivalent) respectively. The PPC showed CMC (critical micelle concentration) of 0.430 mg/mL in distilled water at room temperature. The PPC micelles showed a mean particle size of 215 ± 11 nm with polydispersity index (PDI) of 0.193 ± 0.006. Further, the transmission electron microscope (TEM) results confirmed the self-assembling character of PPC into micelles. The PPC caused significantly less hemolysis (18.6 ± 2.9%) than plain PPT solution. Also, it demonstrated significantly (p < 0.01) higher in vitro cytotoxicity against both sensitive as well as resistance human breast cancer cells (MCF-7 and MDA MB-231) after 48 h of treatment. Conclusion The obtained study results clearly revealed the notable in vitro anticancer activity of PPT following its esterification with PAA. However, further in vivo studies are needed to ascertain its efficacy against a variety of cancers.