Dendrimers for Enhanced Drug Solubilization

Svenson, Sönke; Chauhan, Abhay Singh

doi:10.2217/17435889.3.5.679

Cited by 130 publications

(85 citation statements)

References 76 publications

(102 reference statements)

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“…conformation is usually strongly dependent on pH conditions), and surface functional groups that could possibly discriminate biological targets and enhance drug solubility. [44][45][46][47][48][49][50][51][52] The poly(amidoamine) (PAMAM) dendrimers are the first and most extensively studied family of dendrimers. [44] Figure 1b depicts the threedimensional structure of a model of a 4 th -generation PAMAM (G4-PAMAM).…”

Section: Introductionmentioning

confidence: 99%

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Bellini

Guimarães

Pacheco

et al. 2015

Journal of Molecular Graphics and Modelling

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The association of the anti-tuberculosis drug rifampicin (RIF) with a 4th-generation poly(amidoamine) (G4-PAMAM) dendrimer was investigated by means of molecular dynamics simulations. The RIF load capacity was estimated to be around 20 RIF per G4-PAMAM at neutral pH. The complex formed by 20 RIF molecules and the dendrimer (RIF20-PAMAM) was subjected to 100 ns molecular dynamics (MD) simulations at two different pH conditions (neutral and acidic). The complex was found to be significantly more stable in the simulation at neutral pH compared to the simulation at low pH in which the RIF molecules were rapidly and almost simultaneously expelled to the solvent bulk. The high stability of the RIF-PAMAM complex under physiological pH and the rapid release of RIF molecules under acidic medium provide an interesting switch for drug targeting since the Mycobacterium resides within acidic domains of the macrophage. Altogether, these results suggest that, at least in terms of stability and pH-dependent release, PAMAM-like dendrimers may be considered suitable drug delivery systems for RIF and derivatives.

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Section: Introductionmentioning

confidence: 99%

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Bellini

Guimarães

Pacheco

et al. 2015

Journal of Molecular Graphics and Modelling

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“…At the same time, the nanoparticles is small size improves the dissolution rate and saturation solubility, which altogether results in enhanced in vivo drug performance. Liposomes, dendrimers, and polymeric micelles have been extensively assessed as carrier systems for poorly soluble drugs [90][91][92]. Alternatively, another strategy to enhance drug solubility consists in formulating the therapeutic molecules as nanocrystalline particles [93].…”

Section: Delivery Of Water-insoluble Compoundsmentioning

confidence: 99%

Current Status and Future Prospects for Nanoparticle‐Based Technology in Human Medicine

Sanvicens

Fernández

Salvador

et al. 2011

Nanoplatform‐Based Molecular Imaging

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“…Covalent attachment of drugs to the surface groups via chemical bonds is more stable and offers better control over drug release compared to the encapsulation of a drug within hydrophobic cavities. 11 In the present study, a PAMAM-PTX conjugate functionalized with anti-HER2 TMAB was developed, and the level of specific active targeting of the conjugate to the HER2 receptor both in vitro and in vivo was examined.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

Ma¹,

Zhang²,

Ni³

et al. 2015

IJN

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Background Antibody-dendrimer conjugates have the potential to improve the targeting and release of chemotherapeutic drugs at the tumor site while reducing adverse side effects caused by drug accumulation in healthy tissues. In this study, trastuzumab (TMAB), which binds to human epidermal growth factor receptor 2 (HER2), was used as a targeting agent in a TMAB-polyamidoamine (PAMAM) conjugate carrying paclitaxel (PTX) specifically to cells overexpressing HER2. Methods TMAB was covalently linked to a PAMAM dendrimer via bifunctional polyethylene glycol (PEG). PTX was conjugated to PAMAM using succinic anhydride as a cross-linker, yielding TMAB-PEG-PAMAM-PTX. Dynamic light scattering and transmission electron microscopy were used to characterize the conjugates. The cellular uptake and in vivo biodistribution were studied by fluorescence microscopy, flow cytometry, and Carestream In Vivo FX, respectively. Results Nuclear magnetic resonance spectroscopy demonstrated that PEG, PTX, fluorescein isothiocyanate, and cyanine7 were conjugated to PAMAM. Ultraviolet-visible spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that TMAB was conjugated to PEG-PAMAM. Dynamic light scattering and transmission electron microscopy measurements revealed that the different conjugates ranged in size between 10 and 35 nm and had a spherical shape. In vitro cellular uptake demonstrated that the TMAB-conjugated PAMAM was taken up by HER2-overexpressing BT474 cells more efficiently than MCF-7 cells that expressed lower levels of HER2. Co-localization experiments indicated that TMAB-conjugated PAMAM was located in the cytoplasm. The in vitro cytotoxicity of TMAB-conjugated PAMAM was lower than free PTX due to the slow release of PTX from the conjugate. In vivo targeting further demonstrated that TMAB-conjugated PAMAM accumulated in the BT474 tumor model more efficiently than non-conjugated PAMAM. Conclusion TMAB can serve as an effective targeting agent, and the TMAB-conjugated PAMAM can be exploited as a potential targeted chemotherapeutic drug delivery system for tumors that overexpress HER2.

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Dendrimers for Enhanced Drug Solubilization

Cited by 130 publications

References 76 publications

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Current Status and Future Prospects for Nanoparticle‐Based Technology in Human Medicine

Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

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