Prartana Kewsuwan

Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles.

Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or intrinsic and acquired resistance limits its application in many types of cancer. CXCR4 is a chemokine receptor which implicates in metastasis of cancers including lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear type of low molecular weight CXCR4 antagonist. In this study, we investigated the possibility of using LFC131 conjugated nanoparticles for targeted delivering doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was conjugated to sodium carboxylmethyl cellulose coated poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar basal epithelial cells called A549 cells were higher and faster than that of untargeted nanoparticles. The specificity of CXCR4-mediated internalization of LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4 monoclonal antibody. Cell studies suggested that sustained release of doxorubicin afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and controlled release drug delivery system.

Gamma sterilization of diclofenac sodium loaded- N-trimethyl chitosan nanoparticles for ophthalmic use

This study was conducted to investigate the effect of gamma irradiation on physicochemical properties of N-trimethyl chitosan (TMC), diclofenac sodium (DC) and diclofenac sodium loaded N-trimethylchitosan nanoparticles (DC-TMCNs), and to determine suitable doses of gamma rays for sterilization of DC-TMCNs. Physicochemical properties of TMC, DC and DC-TMCNs before and after exposure to gamma rays at various doses were investigated. It was found that gamma irradiation at doses of 5-25kGy did not cause any significant changes in physical and chemical properties of TMC, DC and DC-TMCNs. The bioburden of DC-TMCNs was 1.5×106 CFU/vial. The initial contaminating bacteria were radiosensitive bacteria. A number of microorganisms was reduced to 10-6 after exposure to 9.9kGy of gamma rays. Therefore, DC-TMCNs could be sterilized by gamma irradiation at a dose of 10kGy, which did not alter their physicochemical properties and did not produce any substances toxic to the eye.

Surface modification of poly(D,L-lactic-co-glycolic acid) nanoparticles using sodium carboxymethyl cellulose as colloidal stabilize.

Poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as drug delivery systems for both small molecules and macromolecules. However, the colloidal stability problem remains unsolved. This study aims to investigate the possibility of using sodium carboxymethyl cellulose (SCMC) as a stabilizing agent of PLGA NPs. In this study, PLGA NPs were fabricated using various concentrations of SCMC (0.01, 0.1 and 0.5% w/v) by solvent displacement method. SCMC coated NPs were characterized using DLS, FTIR, DSC, colorimetric method. Particle size, polydispersity index, zeta potential values and SCMC adsorption increased with SCMC concentration. FTIR spectra, DSC thermograms and results of colorimetry suggested the interaction of SCMC and PLGA NPs. The stability of SCMC coated PLGA NPs was observed during the storage of three weeks in water. The stability of SCMC coated NPs in serum was also evaluated. Cell viability study revealed that there was no toxicity increased when SCMC was used as a stabilizing agent up to a concentration of 0.1% w/v. SCMC coated PLGA NPs bound A549 cells in a time dependent manner and with a greater extent than uncoated PLGA NPs. In conclusion, SCMC can be used to stabilize PLGA NPs by adsorbing on the surface of NPs.

CXCR4-targeted Nanoparticles Reduce Cell Viability, Induce Apoptosis and Inhibit SDF-1α Induced BT-549-Luc Cell Migration In Vitro

BACKGROUND CXCR4 possesses a critical role in several intracellular events such as chemotaxis, invasion and adhesion, which are associated with metastasis of cancer cell. OBJECTIVE In this study, CXCR4 targeted polymeric nanoparticle was developed for delivering cytotoxic drug and blocking the chemokine induced migration of cells expressing CXCR4. METHOD A peptide which was a linear form of CXCR4 antagonist (LFC131) was attached to PLGA nanoparticles (LFC131-NPs) and PLGA nanoparticles encapsulating DOX (LFC131-DOX-NPs). The cellular binding and internalization of LFC131-DOX-NPs were investigated. RESULTS The binding and internalization of LFC131-DOX-NPs were higher and more rapidly compared to unconjugated NPs. LFC131-NPs blocked SDF-1α induced migration of BT-549-Luc cells. MTT assays demonstrated that LFC131-NPs and LFC131-DOX-NPs decreased cell viability in a dose dependent manner in 24, 72 and 120 h incubation. CONCLUSION A treatment concept of blocking breast cancer cell migration from interaction with SDF- 1α by using LFC131-NPs and then attacking breast cancer cells with doxorubicin might increase the efficacy of current breast cancer treatment.