8 research outputs found
Potent Engineered PLGA Nanoparticles by Virtue of Exceptionally High Chemotherapeutic Loadings
Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT® (Particle Replication In Non-wetting Templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere®
Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft
The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system
Potent Engineered PLGA Nanoparticles by Virtue of Exceptionally High Chemotherapeutic Loadings
Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft
The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system
Delivery of Multiple siRNAs Using Lipid-Coated PLGA Nanoparticles for Treatment of Prostate Cancer
Nanotechnology can provide a critical advantage in developing
strategies
for cancer management and treatment by helping to improve the safety
and efficacy of novel therapeutic delivery vehicles. This paper reports
the fabrication of polyÂ(lactic acid-<i>co</i>-glycolic acid)/siRNA
nanoparticles coated with lipids for use as prostate cancer therapeutics
made via a unique soft lithography particle molding process called
Particle Replication In Nonwetting Templates (PRINT). The PRINT process
enables high encapsulation efficiency of siRNA into neutral and monodisperse
PLGA particles (32–46% encapsulation efficiency). Lipid-coated
PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA
in vitro to knockdown genes relevant to prostate cancer