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Title: Fabrication, Characterization, In-Vitro and In-Vivo Evaluation of Etoposide Loaded Polymeric Nanoparticles
Authors: Hassan, Muhammad
Keywords: pharmacy
Issue Date: 2019
Publisher: University of Peshawar, Peshawar.
Abstract: The discovery of biodegradable and biocompatible polymeric materials has a significant step to overcome the problems associated with this field. The polylactic co-glycolide (PLGA) copolymer nanoparticles system in a size range of 10 to 500 nanometers can be used to entrap large number of drugs which have the ability to escape from reticuloendothelial system of the body, the polymeric loaded nanoparticles can remain within the blood circulation for a prolong time and can target the specific site, attached on its surface and release the entrapped therapeutic agent in a controlled and predictable manner. The release of the drug at a specific site or organ of interest can reduce their adverse effects due to the fact that there will be no significant concentration of the drug in blood circulation. Other important features of these polymeric systems are reduced dosing frequency and aqueous solubility which allows the use of these delivery systems effectively for those therapeutic agents which have sever toxic effect as well as having either no or less aqueous solubility. The objective of this work was to develop a PLGA based polymeric delivery system which could entrap Etoposide and enhance its delivery to the organ of interest for a prolonged period of time. The use of etoposide is compromised by its intrinsically poor water solubility as it is BCS class II drug The etoposide Poly(D,L-lactide-co-glycolide) nanoparticles of about 200 nm size were prepared by modified solvent evaporation method while utilizing different surfactants / stabilizing agents which include polyvinyl alcohol (PVA) and Poloxamer 407. The surfactant agents were used in the range of 0.25, 0.5, 1.0 and 1.5 percent concentrations. During the process of formulation of nanosuspensions the concentration of PLGA was kept constant i.e. 15 mg while that of the drug was kept Abstract XVIII as 1, 2, 3, 4 and 5 mg during the preparation of the suspensions. The %EE of the nanoparticles was in the range of 88 to 96%. The nano formulations were characterized in terms of particle size, polydispersibility index (PDI), Zeta potential (ZP), drug entrapment, particle morphology and in-vitro drug release. The size, PDI, ZP and entrapment efficiency of the selected formulations were in the range of (136 182 nm) (0.11-0.30) (-10 to -12) and (88% to 96%) respectively. The drug excipients compatibility was determined by preparing their samples in 1:1 mixture and were kept under stress conditions (45 ± 2 ᴼC and 75 ± 5 % RH) for 90 days and were then analyzed for physical consistency, drug content and FTIR spectra. The compatibility studies show that the drug and excipients used in this study were compatible and no effect of stress condition was observed on the samples. UV Visible Spectrophotometric and High-Performance Liquid Chromatography (HPLC) UV methods were developed and validated for the analysis and determination of Etoposide. The UV-visible spectrophotometric method was specific, accurate and linear in the range of 10-100 µg/ml, with R2 values of 0.998. The RP- HPLC-UV method was novel, sensitive, accurate, specific and validated for the determination of etoposide in physiological fluids. Its linearity was in the concentration range of 12– 1000 ng/ml. The limit of detection (LOD) and limit of quantification (LOQ) were 5 and 12 ng/ml respectively. In-vitro drug release from the NPs was determined by dialysis technique, the NPS were capable to sustained the drug in a predictable manner up to seven (07) days. The distribution of Etoposide NPs in different organs (liver, lungs, kidney, spleen, heart and brain) using mice as an animal model was determined using HPLC-UV method. It was observed that these tissues show the presence of drug for longer duration after administration of drug loaded NPs as compare to reference formulation. Abstract XIX The comparative tissue distribution after intravenous drug loaded NPs administration was in the order of liver > lung > kidney > spleen > heart. In conclusion, the results obtained in the present study showed that PLGA nanoparticles of about 200 nm can be prepared by solvent evaporation method which can encapsulate an anticancer agent etoposide and can release a drug in a sustained manner for up to 168 hours leading to reduction in dosing frequency as well as distributing the drug to the organ of interest. The pharmacokinetic parameters of the nanoformulations are significantly improved as compared to the marketed formulation of etoposide.
Gov't Doc #: 19254
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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