Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives

Beezer, Anthony E.; King, Amy S. H.; Martin, Ian K.; Mitchel, J.C; Twyman, Lance J.; Wain, C.F

doi:10.1016/s0040-4020(03)00437-x

Cited by 210 publications

(170 citation statements)

References 22 publications

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“…3,51 These complexes were found to remain stable at neutral pH conditions, even after storage for several weeks, but they were found unstable in an acidic environment. Attempts for complex formation with nonpolar molecules were proven unsuccessful, 51 suggesting that interactions between the polar regions of the acidic drug and the dendrimer were particularly important for complex formation.…”

Section: Resultsmentioning

confidence: 99%

“…[40][41][42][43] To verify the suitability of the AMBER forcefield for the description of the ibuprofen molecules, we have checked characteristic properties such as the density, the Hansen solubility parameter 44 and the average dipole moment of the drug and compared it to available literature data. Namely, after the NPT MD runs, the density was stabilized at F ) 0.99 ( 0.02 g/cm 3 which compares favorably to a value of 1.06 g/cm 3 , as can be estimated for the amorphous state of ibuprofen, 45,46 whereas calculation of the total Hansen solubility parameter δ based on the cohesive energy density (see, e.g., ref 47 for a more detailed description of the procedure) rendered a value of 9.57 ( 0.46 (cal/cm 3 ) 0.5 , which is within the range of 9.39 to 9.66 (cal/cm 3 ) 0.5 reported for bulk ibuprofen. 48,49 Calculation of the average dipole moment of ibuprofen yielded a value of 1.80 ( 0.02D, which lies within the limits estimated for the more stable ibuprofen conformers.…”

Section: Simulation Detailsmentioning

confidence: 99%

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Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

Tanis

Karatasos

2009

J. Phys. Chem. B

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In this work, we report results from fully atomistic molecular dynamics simulations regarding the associative behavior of a third-generation poly(amidoamine) dendrimer with ibuprofen, a weakly acidic nonsteroidal anti-inflammatory drug, in aqueous solutions and at different pH conditions. Employing a combined static and dynamic approach, we describe the specifics of the complexation/encapsulation of the drug within the dendritic structure. In addition, information regarding the dynamic behavior is provided for the self-and the collective motion of the drug molecules. The detail afforded by the present molecular-level description of the relevant associative mechanisms (i.e., electrostatic complexation, hydrogen-bonding), provides a deeper insight for the interpretation of recent experimental findings regarding the behavior of dendrimer/ibuprofen systems in an aqueous environment.

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Section: Resultsmentioning

confidence: 99%

Section: Simulation Detailsmentioning

confidence: 99%

Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

Tanis

Karatasos

2009

J. Phys. Chem. B

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“…As a result, the branches become entwined as multiplicities increase, producing geometrically-closed nanostructures that can encapsulate small molecule drugs [5]. Notably, drug encapsulation is not limited to physical entrapment; many dendrimers are comprised of internal amines that complex negatively-charged drugs through electrostatic interactions [84], increasing loading capacity relative to poly-alcohols that can only participate in hydrogen bonding [85].…”

Section: Dendrimersmentioning

confidence: 99%

Nanostructured materials for applications in drug delivery and tissue engineering

Goldberg

Langer

Jia

2007

Journal of Biomaterials Science, Polymer Edition

943

554

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Research in the areas of drug delivery and tissue engineering has witnessed tremendous progress in recent years due to their unlimited potential to improve human health. Meanwhile, the development of nanotechnology provides opportunities to characterize, manipulate and organize matter systematically at the nanometer scale. Biomaterials with nano-scale organizations have been used as controlled release reservoirs for drug delivery and artificial matrices for tissue engineering. Drug-delivery systems can be synthesized with controlled composition, shape, size and morphology. Their surface properties can be manipulated to increase solubility, immunocompatibility and cellular uptake. The limitations of current drug delivery systems include suboptimal bioavailability, limited effective targeting and potential cytotoxicity. Promising and versatile nano-scale drug-delivery systems include nanoparticles, nanocapsules, nanotubes, nanogels and dendrimers. They can be used to deliver both small-molecule drugs and various classes of biomacromolecules, such as peptides, proteins, plasmid DNA and synthetic oligodeoxynucleotides. Whereas traditional tissue-engineering scaffolds were based on hydrolytically degradable macroporous materials, current approaches emphasize the control over cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix (ECM). The understanding that the natural ECM is a multifunctional nanocomposite motivated researchers to develop nanofibrous scaffolds through electrospinning or self-assembly. Nanocomposites containing nanocrystals have been shown to elicit active bone growth. Drug delivery and tissue engineering are closely related fields. In fact, tissue engineering can be viewed as a special case of drug delivery where the goal is to accomplish controlled delivery of mammalian cells. Controlled release of therapeutic factors in turn will enhance the efficacy of tissue engineering. From a materials point of view, both the drug-delivery vehicles and tissue-engineering scaffolds need to be biocompatible and biodegradable. The biological functions of encapsulated drugs and cells can be dramatically enhanced by designing biomaterials with controlled organizations at the nanometer scale. This review summarizes the most recent development in utilizing nanostructured materials for applications in drug delivery and tissue engineering.

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“…Multivalent dendrimers are attracting a great deal of interest for applications in biomedical diagnostics [27][28][29][30], pharmacology / drug delivery [31,32] [33], cancer research [34], and nanomedicine [35]. Their use in research is still unabated now, 30 years after their first reported synthesis by Vogtle [36].…”

mentioning

confidence: 99%

A comparison of mono and multivalent linkers and their effect on the colloidal stability of nanoparticle and immunoassays performance

Gubala

Guével

Nooney

et al. 2010

Talanta

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When designing devices for biomedical diagnostics, increasing the signal to noise ratio is often critical for achieving clinically relevant sensitivity and limits of detection (LOD). In antibodybased assays, the measured signal can be amplified through the replacement of molecular fluorophores with doped nanoparticles (NP). However, the benefits of using NPs can only be realized if the NPs are coated efficiently with detection antibody, have good colloidal stability and the ratio of specific to non-specific binding (NSB) is high enough. The main focus of this paper is on the optimization of the bioconjugation protocol for antibody labeling of NPs leading to improved assay performance. Two types of linkers were used: monovalent linkers (glutaraldehyde; sulfo-SMCC; and sulfo-SIAB), and three generations of dendrimers endowed with multivalent carboxylic functionality. Overall, the NP-IgG conjugates prepared using multivalent linkers showed a significantly lower LOD and higher sensitivity than their homo-or hetero-functional counterparts. The multivalent dendrimers also improved NP stability and reduced aggregation. Moreover, the dendrimers showed a higher reactivity with biological material, a feature that could significantly reduce the cost of high-throughput biodiagnostics tests. Introduction:

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Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives

Cited by 210 publications

References 22 publications

Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

Nanostructured materials for applications in drug delivery and tissue engineering

A comparison of mono and multivalent linkers and their effect on the colloidal stability of nanoparticle and immunoassays performance

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