Engineering of blended nanoparticle platform for cellular uptake improvement
9
Issued Date
2019
Resource Type
Language
eng
Rights
Mahidol University
Rights Holder(s)
Faculty of Pharmacy Mahidol University
Suggested Citation
Jiraphong Suksiriworapong, Vincenzo Taresco, Martin C. Garnett, Amaraporn Wongrakpanich, จิรพงศ์ สุขสิริวรพงศ์, อมราพร วงศ์รักษ์พานิช (2019). Engineering of blended nanoparticle platform for cellular uptake improvement. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/49691
Title
Engineering of blended nanoparticle platform for cellular uptake improvement
Other Contributor(s)
Abstract
Over the past decades, a targeted delivery system based on the polymeric nanoparticles
(NPs) gain much interest in cancer therapy. The development of new NPs that can deliver drugs
at a controllable rate directly to cancer cells could potentially improve the efficacy and reduce
the toxicity. However, one of the major barriers of these NPs is their relatively low cellular
uptake and poor penetration into the tumor site.
To address this problem, we have designed a novel nanoparticulate system by blending
two types of polymers; poly(lactic-co-glycolic acid) (PLGA) and poly(glycerol) adipate
conjugated with triphenylphosphonium cation (TPP-PGA). Cationized triphenylphosphonium
cation or TPP was introduced to the system as a moiety to increase penetration and cellular
uptake. In order to obtain TPP-PGA, the PGA was grafted with 10 mol% TPP using a
carbodiimide coupling reaction. The success in grafting of TPP along the polymer backbone
was confirmed via Fourier-transform infrared spectroscopy (FT-IR) and Nuclear magnetic
resonance (NMR) spectra. To prepare the NPs, nanoprecipitation method was used. The
fluorescence probe, rhodamine B and coumarin-6 were used to represents hydrophilic and
lipophilic drug molecules, respectively. Five ratios of blended PLGA and TPP-PGA
(PLGA:TPP-PGA) polymers were prepared at the ratio of (70:30), (80:20), (90:10) and (100:0).
It is worth to note that PLGA:TPP-PGA(100:0) NPs were the NPs prepared solely by PLGA.
The hydrodynamic diameter and zeta potential of prepared NPs were observed using a
Zetasizer nano ZS. Particle morphology was observed using Scanning Electron Microscopy
(SEM). The NPs diameters were in the range between 117-215 nm with low polydispersity
index. The smallest size of NPs was prepared using PLGA:TPP-PGA(100:0) blended ratio.
According to the surface charge, PLGA:TPP-PGA(100:0) NPs had negative surface charge.
When the ratio of TPP-PGA in blended polymers was increased, NPs with the positive surface
charge were obtained. The cellular uptake (in vitro) was conducted in SaOS-2 cells using flow
cytometry and confocal microscopy. Cytotoxicity test was conducted using MTT. Increasing
ratio of TPP-PGA in blended polymers resulted in an increase in the cellular uptake. NPs made
from PLGA:TPP-PGA(70:30) showed highest cellular uptake nevertheless these NPs also
showed the highest cell toxicity.
In this study, a new NPs system made by blending PLGA with TPP-PGA was more
readily taken up by SaOS-2 cells. These particles have potential to be used as a prototype for
targeting delivery in cancer therapy.
Description
The 1st Pharmaceutical Sciences Asia Conference 2019 Theme : Pharmaceutical Sciences toward Health Innovation in the Disruptive Era. Bangkok Midtown Hotel, Thailand. August 22, 2019, page 35