Poly(amido amine) dendrimers in oral delivery

Yellepeddi, Venkata K.; Ghandehari, Hamidreza

doi:10.1080/21688370.2016.1173773

Cited by 41 publications

(27 citation statements)

References 68 publications

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“…Also, anionic PAA polymers have been described as more efficiently transported across the intestinal epithelium, primarily through the paracellular route [7]. However, despite numerous studies on oral PAA bioavailability [6,7,8,9,10], it remains unexplored to what extent this administration method provides the necessary plasma drug concentrations for the pharmaceutical development of oral antimalarial formulations targeting Plasmodium parasites inside red blood cells (RBCs).…”

Section: Introductionmentioning

confidence: 99%

Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

et al. 2018

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Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual Plasmodium stages in the peripheral bloodstream, whereas recommendations for future interventions stress the importance of also targeting the transmission stages of the parasite as it passes between humans and mosquitoes. Orally administered polyamidoamine (PAA) nanoparticles conjugated to chloroquine reached the blood circulation and cured Plasmodium yoelii-infected mice, slightly improving the activity of the free drug and inducing in the animals immunity against malaria. Liquid chromatography with tandem mass spectrometry analysis of affinity chromatography-purified PAA ligands suggested a high adhesiveness of PAAs to Plasmodium falciparum proteins, which might be the mechanism responsible for the preferential binding of PAAs to Plasmodium-infected erythrocytes vs. non-infected red blood cells. The weak antimalarial activity of some PAAs was found to operate through inhibition of parasite invasion, whereas the observed polymer intake by macrophages indicated a potential of PAAs for the treatment of certain coinfections such as Plasmodium and Leishmania. When fluorescein-labeled PAAs were fed to females of the malaria mosquito vectors Anopheles atroparvus and Anopheles gambiae, persistent fluorescence was observed in the midgut and in other insect’s tissues. These results present PAAs as a versatile platform for the encapsulation of orally administered antimalarial drugs and for direct administration of antimalarials to mosquitoes, targeting mosquito stages of Plasmodium.

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Section: Introductionmentioning

confidence: 99%

Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

et al. 2018

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“…Several investigations have been published, aiming to understand and/or improve pharmacokinetic parameters. The major concern is that PAMAM toxicity and biocompatibility are mainly related to the chemical groups that are present on the surface [ 112 ].…”

Section: Biomedical Applicationsmentioning

confidence: 99%

“…Both dendrimers exhibited an increase of 2- to 3-fold intestinal absorption of camptothecin in vivo [ 116 ]. As a conclusion, PAMAM dendrimers can be applied to enhance the intestinal permeability of drugs with poor oral bioavailability, as well as targeting drug delivery [ 112 ].…”

Section: Biomedical Applicationsmentioning

confidence: 99%

New Advances in General Biomedical Applications of PAMAM Dendrimers

et al. 2018

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Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named ‘starburst polymers’. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned.

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“…Poly(amido)amine (PAMAM) dendrimer is a nanosized moiety with highly branched multivalent organic surface that can be used to conjugate multiple drug molecules . A PAMAM drug conjugate can be used to overcome issues associated with solubility and biodistribution to further enhance the overall pharmacodynamic effect . In addition, PAMAM dendrimers have inherent anticancer activity and can be further manipulated to target specific types of cells .…”

Section: Introductionmentioning

confidence: 99%

“…[21] A PAMAM drug conjugate can be used to overcome issues associated with solubility and biodistribution to further enhance the overall pharmacodynamic effect. [22,23] In addition, PAMAM dendrimers have inherent anticancer activity and can be further manipulated to target specific types of cells. [24] Therefore, in this study we synthesized and characterized the anticancer properties of PAMAM-PTX conjugate (PAX) in in vitro models of UGC with variable P53 status.…”

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confidence: 99%

Omega‐3 Fatty Acid Grafted PAMAM‐Paclitaxel Conjugate Exhibits Enhanced Anticancer Activity in Upper Gastrointestinal Cancer Cells

Dichwalkar

Patel

Bapat

et al. 2017

Macromolecular Bioscience

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Upper Gastrointestinal Cancers (UGCs) are a leading cause of cancer-related deaths worldwide. Paclitaxel (PTX) is frequently used for the treatment of UGCs; however, low bioavailability, reduced solubility, and dose-dependent toxicity impede its therapeutic use. PAMAMG -NH -DHA is synthesized by linking amine-terminated fourth-generation poly(amidoamine) (PAMAMG -NH ) dendrimers with omega-3 fatty acid docosahexaenoic acid (DHA). Next, PAMAMG -NH -DHA-PTX (DHATX) and PAMAMG -NH -PTX (PAX) conjugates are synthesized by subsequent covalent binding of PTX with PAMAMG -NH -DHA and PAMAMG -NH , respectively. H-NMR and MALDI-TOF analyses are performed to confirm conjugation of DHA to PAMAMG -NH and PTX to PAMAMG -NH -DHA. The cell viability, clonogenic cell survival, and flow cytometry analyses are used to determine the anticancer activity of PTX, PAX, and DHATX in UGC cell lines. The in vitro data indicate that treatment with DHATX is significantly more potent than PTX or PAX at inhibiting cellular proliferation, suppressing long-term survival, and inducing cell death in UGC cells.

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Poly(amido amine) dendrimers in oral delivery

Cited by 41 publications

References 68 publications

Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs

New Advances in General Biomedical Applications of PAMAM Dendrimers

Omega‐3 Fatty Acid Grafted PAMAM‐Paclitaxel Conjugate Exhibits Enhanced Anticancer Activity in Upper Gastrointestinal Cancer Cells

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