RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

Abstract

Docetaxel (DTX), a cytotoxic taxane, is a poor water-soluble drug and exhibits less oral bioavailability. Current research investigates the effective transport, for DTX-loaded chitosan (CS)-coated-poly-lactide-co-glycolide (PLGA)-nanoparticles (NPs) (DTX-CS-PLGA-NPs) and DTX-PLGA-NPs as well as a novel third-generation P-gp inhibitor i.e. GF120918 (Elacridar), across intestinal epithelium with its successive uptake by the tumour cells in an in vitro model. The prepared NPs showed a spherical shape particle size i.e. <123.96 nm with polydispersity index (PDI) of <0.290 whereas for CS-coated NPs, the zeta potential was converted from negative to positive value along with a small modification in particle size distribution. The entrapment efficiency observed for DTX-CS-PLGA-NPs was 74.77%, whereas the in vitro release profile revealed an initial rapid DTX release followed by a sustained release pattern. For apparent permeability, DTX-CS-PLGA-NPs and DTX-PLGA-NPs along with GF120918 showed a five-fold (p < .01) and 2.2-fold enhancement, respectively, as observed in rat ileum permeation study. Similarly, for pharmacokinetic (PK) studies, higher oral bioavailability was observed from DTX-CS-PLGA-NPs (5.11-folds) and DTX-PLGA-NPs (3.29-folds) as compared with DTX-suspension (DTX-S). Cell uptake studies on A549 cells as performed for DTX-CS-PLGA-NPs and DTX-PLGA-NPs loaded with rhodamine 123 dye, exhibited enhanced uptake as compared with plain dye solution. The enhanced uptake for DTX-CS-PLGA-NPs and DTX-PLGA-NPs formulations in the presence of GF120918 was confirmed further with the help of confocal laser scanning microscopic images (CLSM). The potential of the third-generation novel P-gp inhibitor (GF120918) investigated for the effective delivery of DTX as well as investigation of permeability and uptake studies whereby a strong potential of GF120918 for effective oral delivery was established.

Quantification and Brain Targeting of Eugenol-Loaded Surface Modified Nanoparticles Through Intranasal Route in the Treatment of Cerebral Ischemia

“…The initial particle size for X1 and X2 i. e. 181.3 ± 10.1 and 254.0 ± 18.0 nm, respectively was observed to increase after CS application i. e. 224.5 ± 5.3 and 284.0 ± 9.1 nm, respectively. This increase in particle size is attributed due to high polymer weight of CS as reported [23,52,53,60]. In addition, the particle size for CS-coated NPs also increased and it is suggested due to presence of CS which increases polymer content [61] For EUG-PCL-NPs, a negative zeta potential of -22.31 ± 1.09 (X1) and -28.17 ± 1.04 mV (X2) was observed and the presence of this negative charge over EUG-PCL-NPs surface is reported due to capped polymeric-carboxylic-groups on the surface of NPs.…”

“…The Chitosan coating method was previously described by Badran et al [52] and Ahmad et al [53] for CS-coated-PCL-NPs (CS-PCL-NPs), a particular volume of X1-PCL-NPs and X2-PCL-NPs was incubated (2 h, room temperature) with an equivalent volume of drug i. e. 2 mg/ml CS in acetic acid (65 %) [23,52,53]. The X1-PCL-NPs and X2-PCL-NPs thus obtained were centrifuged, washed two times, redispersed in equal volume of distilled water and stabilized using a freeze dryer at − 60 °C for 3-days (Labconco, TriadTM, Kansas City, MO) (52,53).. All formulations were prepared triplicate.…”

Design of mannosylated oral amphotericin B nanoformulation: efficacy and safety in visceral leishmaniasis

“…One of the objectives of the study was to improve the oral bioavailability of the AmB by enhancing the permeation of the AmB-loaded nanocarriers. It is highly recognized that influx and efflux transporters for instance P-glycoprotein (P-gp) available on the intestinal epithelial cells membrane have a considerable influence on drug absorption [26,27]. Besides P-gp, paracellular route is another pathway which can significantly improve the bioavailability of orally administered drugs and drug-loaded nanocarriers.…”

Microemulsions as Nanotemplates: A Soft and Versatile Approach

“…Ge and co-workers [46] prepared the biodegradable NPs by precipitating the W/O microemulsion (RNA aqueous solution/dichloromethane (poly(L-lactic acid)-poly(ethylene glycol)/n-octyl β-D-glucopyranoside/n-butanol) in supercritical CO 2 . Ahmad et al [47] prepared chitosan coated poly-lactide-coglycolide NPs using O/W microemulsion system and reported better results (entrapment efficiency, in vitro release and in vitro cytotoxicity) than conventional drug solution and unloaded NPs.…”