Browsing by Author "Abhitinder Kumar"

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Development and characterization of micelles for nucleolin-targeted co-delivery of docetaxel and upconversion nanoparticles for theranostic applications in brain cancer therapy
(Editions de Sante, 2023) Mahima Chauhan; Rahul Pratap Singh; Sonali; Bhavna Yadav; Saurabh Shekhar; Abhitinder Kumar; Abhishesh Kumar Mehata; Amit Kumar Nayak; Rohit Dutt; Vandana Garg; Vikas Kailashiya; Madaswamy S. Muthu; Biplob Koch; Dharmendra Kumar Pandey
Despite the existence of several treatment modalities and advancements in cancer research, brain cancer is still incurable. Over-expression of nucleolin receptors on cancer cells has been explored in several studies. The study aimed to develop and characterize nucleolar -targeted theranostic pluronic F127-TPGS micelles for brain cancer therapy. The theranostic agents i.e., Docetaxel; DTX as a therapeutic agent, and the upconversion nanoparticles; UCNP as a diagnostic agent, were loaded into micelles by a slightly-modified solvent casting method. Micelles were further decorated with synthesized TPGS-AS1411 aptamer conjugate for targeting brain cancer cells. The prepared micelles were found between 90 and 165 nm, with a uniform homogeneous and narrow distribution in formulations. DTX and UCNP encapsulation efficiencies of micelles were found 74–88% and 38–40%, respectively. Micelles have depicted sustained release of DTX for as long as 72 h. Hemolytic assay confirmed that DUTP-AS1411 aptamer micelles were found more biocompatible than Taxotere®. The cytotoxicity results revealed that DTP, DUTP, and DUTP-AS1411 aptamer micelles achieved 4.20, 11.70, and 17.54-fold more effectiveness than Taxotere®, after 24 h of therapy, respectively. In addition, DUTP-AS1411 aptamer micelles achieved higher tmax and Cmax of DTX up to 8- and 1.5-fold, respectively, compared to Taxotere® treated group. A similar trend was observed for the brain-distribution study as DUTP-AS1411 aptamer micelles were found more efficacious than Taxotere®. The histopathology studies showed no toxicity and cellular damage even after the 14th and 28th day post i.v. administration of normal saline, DTP, DUTP, and DUTP-AS1411 aptamer micelles formulations whereas Taxotere® has reported to cause toxicity in brain tissues. The study revealed that DUTP-AS1411 aptamer micelles inherit promising and improved therapeutic efficacy, reduced toxicity, dosing frequency, and sustained drug release behavior which can be further exploited as a potential therapeutic approach for brain cancer. © 2023 Elsevier B.V.
RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy
(Elsevier B.V., 2023) Bhavna Yadav; Mahima Chauhan; Saurabh Shekhar; Abhitinder Kumar; Abhishesh Kumar Mehata; Amit Kumar Nayak; Rohit Dutt; Vandana Garg; Vikas Kailashiya; Madaswamy S. Muthu; Sonali; Rahul Pratap Singh
Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100–200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer. © 2023 Elsevier B.V.