Pharmaceutical Sciences and Natural Products

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Polymeric nanoparticles of aromatase inhibitors: A comprehensive review
(Bentham Science Publishers, 2020-09-29T00:00:00) Mishra, Keerti; Ratre, Pooja; Thareja, Suresh; Jain, Akhlesh K.
Being the second most frequent cancer, breast cancer is emerging worldwide with an alarming rate, specifically in post-menopausal women. Targeted drug delivery has been in the focus for the successful treatment of breast cancer by enhancing the drug delivery efficiency and reducing the systemic toxicity of drugs. Al-so, it eliminates the drawbacks associated with conventional chemotherapy, including neuropathy, memory loss, cardiotoxicity and low RBCs count. This review elaborates the polymeric nanoparticles based formulation approaches for selective and sustained delivery for effective cure of breast cancer. However, breast cancer, a life-threatening disease, is mostly caused because of estrogen, thus aromatase inhibitors and estrogen synthesis inhibitors could prevent chances of breast cancer. The disease is associated with drug resistance and some side effects, which could be easily eliminated by using novel therapeutic approaches. Aromatase inhibitors, when en-trapped in nanoparticles, have shown sustained drug release, advocating themselves to be beneficial for the treatment of breast cancer. � 2021 Bentham Science Publishers.
Mannose conjugated starch nanoparticles for preferential targeting of liver cancer
(Bentham Science Publishers, 2020-09-04T00:00:00) Jain, Akhlesh Kumar; Sahu, Hitesh; Mishra, Keerti; Thareja, Suresh
Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site-specific delivery. Background: Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation chal-lenge, it is necessary to develop novel target-specific drug delivery system for the effective and bet-ter localization of drug into the proximity of target with restricting the movement of the drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5--FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and Methods: 5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies. Result and Discussion: 5-Fluorouracil loaded NPs had a particle size between 336 to 802nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorp-hous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer. � 2021 Bentham Science Publishers.
In silico molecular interaction studies of chitosan polymer with aromatase inhibitor: Leads to letrozole nanoparticles for the treatment of breast cancer
(Bentham Science Publishers, 2020-08-26T00:00:00) Mishra, Keerti; Verma, Sant K.; Ratre, Pooja; Banjare, Laxmi; Jain, Abhishek; Thareja, Suresh; Jain, Akhlesh K.
Background: It takes a lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into account for the evaluation of the drug delivery ability of the chitosan nanoparticles. Objective: The present work was aimed to study the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency were carried out. Methods: In the current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically; hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. Results: Letrozole had the second-highest binding affinity within the core of chitosan with MolDock (-102.470) and Re-rank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. Conclusion: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment. � 2021 Bentham Science Publishers.

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