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Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems.

Thukral DK, Dumoga S, Arora S, Chuttani K, Mishra AK - Cancer Nanotechnol (2014)

Bottom Line: This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network.In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX).These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.

View Article: PubMed Central - PubMed

Affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.

ABSTRACT

In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non-cytotoxic nature of these carrier systems. In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help of in vivo studies using radiolabeling techniques (with (99m)Tc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.

No MeSH data available.


Related in: MedlinePlus

In vitro cytotoxicity of PETRA crosslinked PEGDA formulations; PP 1, PP 2 and PP 3 after 48 h of incubation.
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Fig2: In vitro cytotoxicity of PETRA crosslinked PEGDA formulations; PP 1, PP 2 and PP 3 after 48 h of incubation.

Mentions: The in vitro cytotoxicity studies of this system were done by the MTT assay. The formulation was tested for its ability to induce cytotoxicity in V79 fibroblast cells using an assay of mitochondrial activity (MTT assay). After 24, 48, and 72 h of exposure, viability was assessed on the basis of cellular conversion of MTT into a formazan product. A plot of percentage viability against the concentration revealed a decrease in the mitochondrial activity of the nanoformulation with increased concentration of upto 1000 μM (Figure 2). Even after 48 h of incubation, the formulations appeared to be non-toxic upto very high concentrations of almost 800 μM. These results suggested that the PETRA crosslinked nanoparticles of PEGDA are nontoxic to normal cells which confirmed their safety for non-cancerous cells. Of these PETRA crosslinked formulations, PP1, which formed the smallest size of nanoparticles, was taken as the matrix based system for further drug loading and biological evaluations. The anticancer activity of the free MTX and MTX loaded PP1 (M-PP1) was studied on MCF-7 breast cancer cells. MTT assay showed that both the free drug and the drug loaded nanoformulation could significantly suppress MCF-7 cell proliferation in a dose and time dependent manner (Figure 3a-c). While at the same concentration, the MTX loaded PP1 showed significantly higher inhibition rates against MCF-7 cells compared to free MTX especially at higher time points of 24 h and 48 h. In this the unloaded nanoformulation (U-PP1) was taken as the control and it was found to show negligible effect on cell viability (Figure 3). Thus the cytotoxicity of the MTX loaded nanoformulations was confirmed to be because of the encapsulated MTX.Figure 2


Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems.

Thukral DK, Dumoga S, Arora S, Chuttani K, Mishra AK - Cancer Nanotechnol (2014)

In vitro cytotoxicity of PETRA crosslinked PEGDA formulations; PP 1, PP 2 and PP 3 after 48 h of incubation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631724&req=5

Fig2: In vitro cytotoxicity of PETRA crosslinked PEGDA formulations; PP 1, PP 2 and PP 3 after 48 h of incubation.
Mentions: The in vitro cytotoxicity studies of this system were done by the MTT assay. The formulation was tested for its ability to induce cytotoxicity in V79 fibroblast cells using an assay of mitochondrial activity (MTT assay). After 24, 48, and 72 h of exposure, viability was assessed on the basis of cellular conversion of MTT into a formazan product. A plot of percentage viability against the concentration revealed a decrease in the mitochondrial activity of the nanoformulation with increased concentration of upto 1000 μM (Figure 2). Even after 48 h of incubation, the formulations appeared to be non-toxic upto very high concentrations of almost 800 μM. These results suggested that the PETRA crosslinked nanoparticles of PEGDA are nontoxic to normal cells which confirmed their safety for non-cancerous cells. Of these PETRA crosslinked formulations, PP1, which formed the smallest size of nanoparticles, was taken as the matrix based system for further drug loading and biological evaluations. The anticancer activity of the free MTX and MTX loaded PP1 (M-PP1) was studied on MCF-7 breast cancer cells. MTT assay showed that both the free drug and the drug loaded nanoformulation could significantly suppress MCF-7 cell proliferation in a dose and time dependent manner (Figure 3a-c). While at the same concentration, the MTX loaded PP1 showed significantly higher inhibition rates against MCF-7 cells compared to free MTX especially at higher time points of 24 h and 48 h. In this the unloaded nanoformulation (U-PP1) was taken as the control and it was found to show negligible effect on cell viability (Figure 3). Thus the cytotoxicity of the MTX loaded nanoformulations was confirmed to be because of the encapsulated MTX.Figure 2

Bottom Line: This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network.In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX).These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.

View Article: PubMed Central - PubMed

Affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.

ABSTRACT

In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non-cytotoxic nature of these carrier systems. In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help of in vivo studies using radiolabeling techniques (with (99m)Tc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.

No MeSH data available.


Related in: MedlinePlus