Role of non-covalent and covalent interactions in cargo loading capacity and stability of polymeric micelles

Ke, Xiyu; Ng, Victor Wee Lin; Ono, Robert J.; Chan, Julian M. W.; Krishnamurthy, Sangeetha; Wang, Ying; Hedrick, James L.; Yang, Yi Yan

doi:10.1016/j.jconrel.2014.06.061

Cited by 112 publications

(59 citation statements)

References 157 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33 In this particular instance, the conjugation of the FA and CS is initiated due to the strong electrostatic interaction of the cationic amino groups of CS with the anionic carboxylate group of FA; the result shows a loading efficiency of approximately 30.5±1.2 wt.%. 33 Despite the successes recorded following noncovalent method of conjugation of FA to other biomolecules or MNPs, [29][30][31][32][33][34] several work reported a superior performance following covalent methods of interactions. 4,35,36 However, the greatest challenge is meeting the requirements of specific conjugation chemistry that retains QDs biochemical activity as much as possible.…”

mentioning

confidence: 99%

Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

Bwatanglang¹,

Mohammad²,

Yusof³

et al. 2016

IJN

View full text Add to dashboard Cite

In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn 2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging.

show abstract

mentioning

confidence: 99%

Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

Bwatanglang¹,

Mohammad²,

Yusof³

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…PEG, which should allow optimal interaction of the folate group and FR (to evaluate in future work). F-PEG-HMD nanomicelles should be at least as stable as most of the lipopolymer conjugates already described (24)(25)(26)46), considering its relatively low CMC value. High stability of the micelles after in vivo administration resulting from, among other characteristics, the CMC value is an important point to consider in order to guarantee their integrity (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…CmC (in a defined solvent) is an important characteristic of self-assembled copolymers because it relates to the stability of the micelles formed in a medium (24)(25)(26)46). Below this CMC, the copolymer will be present in the solvent as a solubilized single copolymer chain.…”

Section: Synthesis a Nd Characterization Of F-pe G -Hm Dmentioning

confidence: 99%

New dry powders for inhalation containing temozolomide-based nanomicelles for improved lung cancer therapy

Rosière

Gelbcke

Mathieu

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Besides the numerous advantages of a chemotherapy administered by the inhalation route for lung cancer therapy, dry powder for inhalation (DPI) offers many advantages compared to other techniques and seems to be a technique that is well-adapted to an anticancer treatment. DPI formulations were developed using the cytotoxic drug temozolomide and a new folate-grafted self-assembling copolymer, a conjugate of three components, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD). F-PEG-HMD was synthesized using carbodiimide-mediated coupling chemistry in three main steps. F-PEG-HMD was characterized by 1 H-NMR, mass spectrometry and thermal analysis. F-PEG-HMD presented a critical micellar concentration in water of 4x10 -7 M. F-PEG-HMD nanomicelles were characterized by a trimodal particle size distribution with Z-average diameter of 83±1 nm in water. Temozolomide-loaded nanomicelles were prepared by solubilization of F-PEG-HMD in the presence of temozolomide. Temozolomide solubility in water was increased in the presence of F-PEG-HMD (2-fold increase in molar solubility) which could potentially lead to increased local concentrations in the tumor site. The temozolomideloaded F-PEG-HMD nanomicelles were characterized by a Z-average diameter of ~50 to ~60 nm, depending on the F-PEG-HMD concentration used. The nanomicelles were then spray-dried to produce dry powders. Temozolomide remained stable during all the formulation steps, confirmed by similar in vitro anticancer properties for the DPI formulations and a raw temozolomide solution. Two of the developed DPI formulations were characterized by good aerodynamic properties (with a fine particle fraction of up to 50%) and were able to release the F-PEG-HMD nanomicelles quickly in aqueous media. Moreover, in vitro, the two DPI formulations showed wide pulmonary deposition in the lower respiratory tract where adenocarcinomas are more often found. The present study, therefore, shows that F-PEG-HMD-based dry powders for inhalation could constitute an interesting drug delivery system able to release nanomicelles that are useful in adenocarcinomas that overexpress folate receptors.

show abstract

“…The better encapsulation efficiency of crosslinked micelles could be attributed to a more tightly packed core with interconnected networks of crosslinked bridges providing more effective diffusion barriers to egress of MTX from the formulation. Various factors have been reported to influence drug loading of polymeric micelles including polymer-drug compatibility, 42 size of the micelle core, 43 presence and extent of micellar crosslinking, presence of specific functional groups in the copolymer, 44 and molecular weight and chemical structure of the encapsulated agents. From the in vitro release experiments (Fig.…”

Section: Discussionmentioning

confidence: 99%

Bioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells

et al. 2017

View full text Add to dashboard Cite

Polymer micelles have emerged as promising carriers for controlled release applications, however, several limitations of micelle-based drug delivery have also been reported. To address these issues, we have synthesized a functional biodegradable and cytocompatible block copolymer based on methoxypoly(ethyleneglycol)-b-poly(ε-caprolactone-co-α-azido-ε-caprolactone) (mPEG-b-poly(εCL-co-αN3εCL)) as a precursor of reduction sensitive core-crosslinked micelles. The synthesized polymer was formulated as micelles using a dialysis method and loaded with the anti-inflammatory and anticancer drug methotrexate (MTX). The micellar cores were subsequently crosslinked at their pendant azides by a redoxresponsive bis(alkyne). The size distributions and morphology of the polymer micelles were assessed using dynamic light scattering (DLS) and transmission electron microscopy, and drug release assays were performed under simplified (serum free) physiological and reductive conditions. Cellular uptake studies in human breast cancer cells were performed using Oregon-green loaded core-crosslinked micelles. The MTX-loaded core-crosslinked micelles were assessed for their effects on metabolic activity in human breast cancer (MCF-7) cells by evaluating the reduction of the dye MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The apoptosis inducing potential of MTX-loaded core-crosslinked micelles was analysed using Hoechst/propidium iodide (PI) and annexin-V/PI assays. The data from these experiments indicated that drug release from these cross-linked micelles can be controlled and that the redox-responsive micelles are more effective carriers for MTX than non-crosslinked analogues and the free drug in the cell-lines tested.

show abstract

Role of non-covalent and covalent interactions in cargo loading capacity and stability of polymeric micelles

Cited by 112 publications

References 157 publications

Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

New dry powders for inhalation containing temozolomide-based nanomicelles for improved lung cancer therapy

Bioreducible cross-linked core polymer micelles enhance in vitro activity of methotrexate in breast cancer cells

Contact Info

Product

Resources

About