Limits...
Synthesis, characterization, and in vivo efficacy evaluation of PGG-docetaxel conjugate for potential cancer chemotherapy.

Yang D, Van S, Shu Y, Liu X, Ge Y, Jiang X, Jin Y, Yu L - Int J Nanomedicine (2012)

Bottom Line: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX.However, PGG-DTX showed better antitumor activity in NCI-H460 lung cancer-bearing mice with minimal weight loss compared to that of free DTX.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China.

ABSTRACT

Aim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamylglutamine) (PGG)-docetaxel (DTX) conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.

Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG-DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.

Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80(®) at 0.4 mg/mL, and 33% for Cremophor EL(®) at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration-dependent manner. However, PGG-DTX showed better antitumor activity in NCI-H460 lung cancer-bearing mice with minimal weight loss compared to that of free DTX.

Conclusion: The PGG-DTX conjugate may be considered as an attractive and promising polymeric DTX conjugate for non-small cell lung cancer treatment.

Show MeSH

Related in: MedlinePlus

Tapping mode atomic force microscopy image of the poly(L-γ-glutamyl-glutamine)– docetaxel conjugate.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3278226&req=5

f3-ijn-7-581: Tapping mode atomic force microscopy image of the poly(L-γ-glutamyl-glutamine)– docetaxel conjugate.

Mentions: The nanoparticle size and size distribution were measured by DLS. As depicted in Figure 2, the mean size of PGG–DTX nanoparticle dispersion was about 30 nm. The conjugate exhibited unimodal particle size distribution with a low polydispersity index of 0.225, which indicated that the dispersion was homogeneous. The average particle size and distribution of the PGG–DTX conjugate were confirmed by TEM and AFM that were used to directly visualize the size and morphology of the PGG–DTX conjugate in the dry state (Figures 2 and 3), showing the nanoparticles were spherical with diameters around 20–30 nm. The particle size of the PGG–DTX conjugate was consistent with the particle size of the PGG–paclitaxel conjugate, which was previously reported.36,37 Zeta potential or particle surface charge is an important parameter, indicating the stability of nanocarrier systems. A relatively high surface charge may provide a repelling force between the particles, thus they could be more stable in solution due to less aggregation.38Table 1 shows that the PGG–DTX conjugate had high negative zeta potentials of −21.3 mV due to the presence of two ionized carboxylic acid groups in the PGG polymer backbone. It is reasonable to conclude that the charged particles may repel each other and prevent aggregation or precipitation.


Synthesis, characterization, and in vivo efficacy evaluation of PGG-docetaxel conjugate for potential cancer chemotherapy.

Yang D, Van S, Shu Y, Liu X, Ge Y, Jiang X, Jin Y, Yu L - Int J Nanomedicine (2012)

Tapping mode atomic force microscopy image of the poly(L-γ-glutamyl-glutamine)– docetaxel conjugate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3278226&req=5

f3-ijn-7-581: Tapping mode atomic force microscopy image of the poly(L-γ-glutamyl-glutamine)– docetaxel conjugate.
Mentions: The nanoparticle size and size distribution were measured by DLS. As depicted in Figure 2, the mean size of PGG–DTX nanoparticle dispersion was about 30 nm. The conjugate exhibited unimodal particle size distribution with a low polydispersity index of 0.225, which indicated that the dispersion was homogeneous. The average particle size and distribution of the PGG–DTX conjugate were confirmed by TEM and AFM that were used to directly visualize the size and morphology of the PGG–DTX conjugate in the dry state (Figures 2 and 3), showing the nanoparticles were spherical with diameters around 20–30 nm. The particle size of the PGG–DTX conjugate was consistent with the particle size of the PGG–paclitaxel conjugate, which was previously reported.36,37 Zeta potential or particle surface charge is an important parameter, indicating the stability of nanocarrier systems. A relatively high surface charge may provide a repelling force between the particles, thus they could be more stable in solution due to less aggregation.38Table 1 shows that the PGG–DTX conjugate had high negative zeta potentials of −21.3 mV due to the presence of two ionized carboxylic acid groups in the PGG polymer backbone. It is reasonable to conclude that the charged particles may repel each other and prevent aggregation or precipitation.

Bottom Line: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX.However, PGG-DTX showed better antitumor activity in NCI-H460 lung cancer-bearing mice with minimal weight loss compared to that of free DTX.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China.

ABSTRACT

Aim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamylglutamine) (PGG)-docetaxel (DTX) conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.

Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG-DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.

Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80(®) at 0.4 mg/mL, and 33% for Cremophor EL(®) at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration-dependent manner. However, PGG-DTX showed better antitumor activity in NCI-H460 lung cancer-bearing mice with minimal weight loss compared to that of free DTX.

Conclusion: The PGG-DTX conjugate may be considered as an attractive and promising polymeric DTX conjugate for non-small cell lung cancer treatment.

Show MeSH
Related in: MedlinePlus