Critical Process Parameters Evaluation of Modified Nanoprecipitation Method on Lomustine Nanoparticles and Cytostatic Activity Study on L132 Human Cancer Cell Line

Abstract

This work was focused on identification and evaluation of process parameters of modified nanoprecipitation method, for fabrication of lomustine nanoparticles, with the aim of reducing cancer cell viability at low concentration of lomustine. The parameters controlling particle size, mostly in nanosize, were solvent/nonsolvent composition and emulsification speed of homogenizer along with aqueous phase volume. This controlled particle size is below 250 nm. The stabilizer concentration controlled particle size is within 68 nm ± 0.89 to 137 ± 0.94 nm with PDI 0.06 ± 0.008 to 0.25 ± 0.001. But, the stabilizer addition mode showed more uniform size distribution with PDI 0.085 ± 0.004. Entrapment efficiency was maintained well above 47 ± 0.23%. The drug release pattern was monophasic with controlled release over 24 hrs. In the method used, drug content was affected by ratio of polymer to drug to organic solvent, as well as homogenization speed and time. Percentage viable cells of L132 human lung cancer cell line remained, were only 5% at 100 µg/ml lomustine equivalent PLA nanoparticles. ethanol as a cosolvent, homogenization speed and time were evaluated affecting the particle size, encapsulation efficiency and in vitro drug release.

Preparation and Characterization and Biodistribution Studies of Lomustine Loaded PLGA Nanoparticles by Interfacial Deposition Method

“…Particle size, polydispersity index (PDI), zeta potential and scanning electron microscopy (SEM): The method used by Mehrotra and Pandit [10] was used. The Zetasizer used was of Malvern instruments, UK DTS Ver 5.10 and SEM was performed on Hitachi Japan S-3400N.…”

“…In-vitro drug release study: The method published by Mehrotra and Pandit [10] was used. Here all method is similar only lomustine was determined by dialysis method using Franz diffusion cell.…”

“…The method used by Mehrotra and Pandit [10] was used here. The nanoparticle formulations used were of batches PD1, PD4 and PD13 based on particle size, physical stability and drug release data.…”

Fabrication of Fucoxanthin-Loaded Microsphere(F-LM) By Two Steps Double-Emulsion Solvent Evaporation Method and Characterization of Fucoxanthin before and after Microencapsulation

“…Mehrotra and Pandit 37 reported that high stirring rate enhanced mass transfer and rate of diffusion between the phases, which induced homogenous supersaturation and rapid nucleation to produce smaller sized microspheres. Thus, increasing homogenization speed decreased the size of the microsphere.…”

Enhanced anticancer properties of lomustine in conjunction with docosahexaenoic acid in glioblastoma cell lines

“…To reduce the toxicity associated with high doses of lomustine, investigators have used nanoparticle technology to more efficiently deliver lower effective doses to the cellular target. 23,24 Numerous clinical trials have revolved around the use of lomustine or temozolomide in conjunction with additional therapeutic reagents, including, but not limited to, antibodies and pharmacological inhibitors. 2,43,45 Despite these attempts to markedly improve clinical outcomes, relatively few gains have been made in extending survival curves or drastically reducing the cytotoxicity associated with the use of these chemotherapeutic reagents.…”