Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies
Oleanolic acid (OA), which is a natural pentacyclic terpenoid, has been identified for hepato-protective, nephron-protective and cardio-tonic properties. In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a question mark because of its known cardio-toxicity. We developed...
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2018-09-01
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author | Muhammad Sarfraz Attia Afzal Tan Yang Yongkang Gai Shahid Masood Raza Muhammad Waseem Khan Yao Cheng Xiang Ma Guangya Xiang |
author_facet | Muhammad Sarfraz Attia Afzal Tan Yang Yongkang Gai Shahid Masood Raza Muhammad Waseem Khan Yao Cheng Xiang Ma Guangya Xiang |
author_sort | Muhammad Sarfraz |
collection | DOAJ |
description | Oleanolic acid (OA), which is a natural pentacyclic terpenoid, has been identified for hepato-protective, nephron-protective and cardio-tonic properties. In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a question mark because of its known cardio-toxicity. We developed a combined nanoliposomal formulation of DOX with OA, as adjuvant, to overwhelm toxic effects of DOX without compromising anticancer activity. The entrapment efficiency and the particle size were brought in limit by the reengineered ethanolic injection method (REIM), without further extrusion. The developed formulations were stable over the study period of two months. A modified HPLC method was employed for the analysis of OA (drug retention time, Tr = 12 ± 1 min). The recovery of OA against spiked plasma samples was more than 90%. MTT assay showed anti-apoptotic synergism against HepG2 cells at non-fixed ratio (combination index, CI < 1). A sustained in vivo drug release of experimental drugs was depicted over 24 h. Histopathological examination and laboratory findings indicated no visible sign of toxicity in the treated mice group against combined delivery. Hence, this combined nanoliposomal formulation was tagged as a safer therapy for the DOX based cancer treatments. |
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spelling | doaj.art-e61b4fa0928b42a899a42068a7ed428f2022-12-22T02:59:09ZengMDPI AGPharmaceutics1999-49232018-09-0110315110.3390/pharmaceutics10030151pharmaceutics10030151Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic StudiesMuhammad Sarfraz0Attia Afzal1Tan Yang2Yongkang Gai3Shahid Masood Raza4Muhammad Waseem Khan5Yao Cheng6Xiang Ma7Guangya Xiang8School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, ChinaOleanolic acid (OA), which is a natural pentacyclic terpenoid, has been identified for hepato-protective, nephron-protective and cardio-tonic properties. In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a question mark because of its known cardio-toxicity. We developed a combined nanoliposomal formulation of DOX with OA, as adjuvant, to overwhelm toxic effects of DOX without compromising anticancer activity. The entrapment efficiency and the particle size were brought in limit by the reengineered ethanolic injection method (REIM), without further extrusion. The developed formulations were stable over the study period of two months. A modified HPLC method was employed for the analysis of OA (drug retention time, Tr = 12 ± 1 min). The recovery of OA against spiked plasma samples was more than 90%. MTT assay showed anti-apoptotic synergism against HepG2 cells at non-fixed ratio (combination index, CI < 1). A sustained in vivo drug release of experimental drugs was depicted over 24 h. Histopathological examination and laboratory findings indicated no visible sign of toxicity in the treated mice group against combined delivery. Hence, this combined nanoliposomal formulation was tagged as a safer therapy for the DOX based cancer treatments.http://www.mdpi.com/1999-4923/10/3/151oleanolic aciddoxorubicinpegylated liposomesreengineered ethanolic injection methodcardiotoxicity |
spellingShingle | Muhammad Sarfraz Attia Afzal Tan Yang Yongkang Gai Shahid Masood Raza Muhammad Waseem Khan Yao Cheng Xiang Ma Guangya Xiang Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies Pharmaceutics oleanolic acid doxorubicin pegylated liposomes reengineered ethanolic injection method cardiotoxicity |
title | Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies |
title_full | Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies |
title_fullStr | Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies |
title_full_unstemmed | Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies |
title_short | Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies |
title_sort | development of dual drug loaded nanosized liposomal formulation by a reengineered ethanolic injection method and its pre clinical pharmacokinetic studies |
topic | oleanolic acid doxorubicin pegylated liposomes reengineered ethanolic injection method cardiotoxicity |
url | http://www.mdpi.com/1999-4923/10/3/151 |
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