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      Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies

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          Abstract

          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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          Nanoencapsulation, Nano-guard for Pesticides: A New Window for Safe Application.

          Md Nuruzzaman, Mohammad Rahman, Yanju Liu … (2016)
          The application of nanotechnology in pesticide delivery is relatively new and in the early stages of development. This technology aims to reduce the indiscriminate use of conventional pesticides and ensure their safe application. This critical review investigated the potential of nanotechnology, especially the nanoencapsulation process for pesticide delivery. In-depth investigation of various nanoencapsulation materials and techniques, efficacy of application, and current research trends are also presented. The focus of ongoing research was on the development of a nanoencapsulated pesticide formulation that has slow releasing properties with enhanced solubility, permeability, and stability. These properties are mainly achieved through either protecting the encapsulated active ingredients from premature degradation or increasing their pest control efficacy for a longer period. Nanoencapsulated pesticide formulation is able to reduce the dosage of pesticides and human exposure to them, which is environmentally friendly for crop protection. However, lack of knowledge of the mechanism of synthesis and lack of a cost-benefit analysis of nanoencapsulation materials hindered their application in pesticide delivery. Further investigation of these materials' behavior and their ultimate fate in the environment will help the establishment of a regulatory framework for their commercialization. The review provides fundamental and critical information for researchers and engineers in the field of nanotechnology and especially the use of nanoencapsulation techniques to deliver pesticides.
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            Nanoparticle-assisted combination therapies for effective cancer treatment.

            Che-Ming Jack Hu, Liangfang Zhang, Santosh Aryal (2010)
            Combination chemotherapy and nanoparticle drug delivery are two areas that have shown significant promise in cancer treatment. Combined therapy of two or more drugs promotes synergism among the different drugs against cancer cells and suppresses drug resistance through distinct mechanisms of action. Nanoparticle drug delivery, on the other hand, enhances therapeutic effectiveness and reduces side effects of the drug payloads by improving their pharmacokinetics. These two active research fields have been recently merged to further improve the efficacy of cancer therapeutics. This review article summarizes the recent efforts in developing nanoparticle platforms to concurrently deliver multiple types of drugs for combination chemotherapy. We also highlight the challenges and design specifications that need to be considered in optimizing nanoparticle-based combination chemotherapy.
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              Drug synergism: its detection and applications.

              R Tallarida (2001)
              Two drugs that produce overtly similar effects will sometimes produce exaggerated or diminished effects when used concurrently. A quantitative assessment is necessary to distinguish these cases from simply additive action. This distinction is based on the classic pharmacologic definition of additivity that, briefly stated, means that each constituent contributes to the effect in accord with its own potency. Accordingly, the relative potency of the agents, not necessarily constant at all effect levels, allows a calculation using dose pairs to determine the equivalent of either agent and the effect by using the equivalent in the dose-response relation of the reference compound. The calculation is aided by a popular graph (isobologram) that provides a visual assessment of the interaction but also requires independent statistical analysis. The latter can be accomplished from calculations that use the total dose in a fixed-ratio combination along with the calculated additive total dose for the same effect. Different methods may be used, and each is applicable to experiments in which a single drug is given at two different sites. When departures from additivity are found, whether in "two-drug" or "two-site" experiments, the information is useful in designing new experiments for illuminating mechanisms. Several examples, mainly from analgesic drug studies, illustrate this application. Even when a single drug (or site) is used, its introduction places it in potential contact with a myriad of chemicals already in the system, a fact that underscores the importance of this topic in other areas of biological investigation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceutics
                Journal ID (iso-abbrev): Pharmaceutics
                Journal ID (publisher-id): pharmaceutics
                Title: Pharmaceutics
                Publisher: MDPI
                ISSN (Electronic): 1999-4923
                Publication date (Electronic): 06 September 2018
                Publication date Collection: September 2018
                Volume: 10
                Issue: 3
                Electronic Location Identifier: 151
                Affiliations
                [1 ]School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, Hubei, China; chiefpharm@ 123456gmail.com (M.S.); attiapharm@ 123456gmail.com (A.A.); yangtan0120@ 123456163.com (T.Y.); gykmail@ 123456gmail.com (Y.G.); shahipharmacist@ 123456gmail.com (S.M.R.); khanwaseem6065@ 123456gmail.com (M.W.K.); cheng_yao@ 123456wuxiapptec.com (Y.C.)
                [2 ]International Joint Laboratory of Nuclear Protein, Henan University, Kaifeng 475001/475004, Henan, China
                [3 ]Faculty of Pharmacy, The University of Lahore (UOL), Lahore 56400, Punjab, Pakistan
                [4 ]Institute of Pharmacy, Lahore College for Women University (LCWU), Lahore 54610, Punjab, Pakistan
                Author notes
                [* ]Correspondence: xiangma@ 123456hust.edu.cn (X.M.); youjiti@ 123456mails.tjmu.edu.cn (G.X.); Tel.: +86-139-8603-2181 (X.M.); +86-27-8369-2793 (G.X.)
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: pharmaceutics-10-00151
                DOI: 10.3390/pharmaceutics10030151
                PMC ID: 6161256
                PubMed ID: 30200557
                SO-VID: 0567d574-1b9f-4f8f-ad40-4cd8c61f89c0
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 04 July 2018
                Date accepted : 31 August 2018
                Categories
                Subject: Article

                Keywords: oleanolic acid,doxorubicin,pegylated liposomes,reengineered ethanolic injection method,cardiotoxicity
                Data availability:
                Keywords: oleanolic acid, doxorubicin, pegylated liposomes, reengineered ethanolic injection method, cardiotoxicity

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