Dendrimers as Carriers for Delivery of Chemotherapeutic Agents

Medina, Scott H.; El-Sayed, Mohamed

doi:10.1021/cr900174j

Cited by 635 publications

(483 citation statements)

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“…One family of potential delivery vehicles are dendrimers which are monodispersed polymers, spherical in shape and which are be easily functionalised with a range of biologically relevant groups (NH 2 or COOH), making them ideal for drug delivery applications [7][8][9]. The number of surface groups on a dendrimer is dependent on the number of cascading branches;…”

Section: Introductionmentioning

confidence: 99%

Evaluation of anionic half generation 3.5–6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin

Kirkpatrick

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Sutcliffe

et al. 2011

Journal of Inorganic Biochemistry

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Title: Evaluation of anionic half generation 3.5-6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin Article Type: Regular Paper Keywords: cancer; platinum; PAMAM dendrimer; cisplatin; guanosine; cytotoxicity; diffusion NMR. Abstract: Aquated cisplatin was added to half-generation PAMAM dendrimers and the resultant complexes were purified by centrifuge. The drug-dendrimer complexes were then characterised by 1-D and diffusion 1H NMR y and ICP-AES. The amount of drug bound was found to increase in proportion with dendrimer size: G3.5, 22 cis-{Pt(NH3)2}molecules per dendrimer; G4.5, 37; G5.5, 54; and G6.5, 94, which represent only a fraction of the available binding sites on each dendrimer (68, 58, 42 and 37%, respectively). Drug release studies showed that some drug remains bound to the dendrimer even after prolonged incubation with 5'GMP at temperatures of 60 oC for over a week (percentage of drug released 18, 30, 35 and 63%, respectively). Attachment of the drug was found to decrease the radius of the dendrimers. Finally, the effect of the dendrimer on drug cytotoxicity was determined using in vitro assays with the A2780, A2780cis and A2780cp ovarian cancer cell lines. The free dendrimers display no cytotoxicity whilst the drug-dendrimer complexes showed moderate activity. In vivo activity was examined using an A2780 tumour xenograft. Cisplatin, at its maximum tolerated dose of 6 mg/kg, reduced tumour size by 33% compared to an untreated control group. The G6.5 cisplatin-dendrimer complex was administered at two doses (6 and 8 mg/kg equivalent of cisplatin). Both were well tolerated by the mice. The lower dose displayed comparable activity to cisplatin with a tumour volume reduction of 32%, but the higher dose was significantly more active than free cisplatin with a tumour reduction of 45%. We have revised the manuscript taking into account all your listed corrections and stylistic requirements.As siDNA and PBS were used only once in the manuscript we have now written these in full and not used them as abbreviations.For simplicity, we have made figure 5 just black and white and have changed the figure caption to reflect this. G4.5, 37; G5.5, 54; and G6.5, 94, which represent only a fraction of the available binding sites on each dendrimer (68, 58, 42 and 37%, respectively). Drug release studies showed that some drug remains bound to the dendrimer even after prolonged incubation with 5'GMP at temperatures of 60 o C for over a week (percentage of drug released 18, 30, 35 and 63%, respectively). Attachment of the drug was found to decrease the radius of the dendrimers. Finally, the effect of the dendrimer on drug cytotoxicity was determined using in vitro assays with the A2780, A2780cis and A2780cp ovarian cancer cell lines. The free dendrimers display no cytotoxicity whilst the drug-dendrimer complexes showed moderate activity. In vivo activity was examined using an A2780 tumour xenograft. Cisplatin, at its maximum tolerated dose of 6 mg/kg, reduced tu...

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Section: Introductionmentioning

confidence: 99%

Evaluation of anionic half generation 3.5–6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin

Kirkpatrick

Plumb

Sutcliffe

et al. 2011

Journal of Inorganic Biochemistry

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“…Major applications are related to the drug delivery systems development (Gillies, Fréchet, 2005;Medina, El-Sayed, 2009;Nanjwade et al, 2009;Wijagkanalan, Kawakami, Hashida, 2011;, solubility (Devarakonda, Hill, Villiers, 2004) and biocompatibility improvements (reduce toxicity) (Duncan, Izzo, 2005;Sadekar, Ghandehari, 2010;Ciolkowski et al, 2012), magnetic resonance image (MRI) contrast (Wiener et al, 1994;Margerum et al, 1997;Kobayashi et al, 2003;Kojima et al, 2011;Tang et al, 2012), targeted drug delivery (Yang et al, 2009;Menjoge et al, 2011) and gene delivery (Dufès, Uchegbu, Schätzlein, 2005;Kim et al, 2007;Mintzer, Simanek, 2009;Shcharbin, Klajnert, Bryszewska, 2009;Nam et al, 2012).…”

Section: Dendrimers As a Platform For No Transportmentioning

confidence: 99%

Nitric oxide releasing-dendrimers: an overview

Roveda

Franco

2013

Braz. J. Pharm. Sci.

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Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.

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“…viscosity (Fréchet et al, 1996,Jikei and Kakimoto 2001, Aulenta, 2003. Due to these unique features this class of polymeric nanomaterial have various applications in different fields like as drug delivery (Florence, 2005, Gillies and Fréchet, 2005, Emanuele and Attwood, 2005, Wolinsky and Grinstaff, 2008, Medina and El-Sayed, 2009), dendrimer based nanomedicine (Majoros and Baker 2008), gene delivery (Mintzer and Simanek, 2009), light harvesting (Adronov and Frechet, 2000), dendritic nanomaterials (Grimsdale and Mullen 2005), electrode design (Guldi and Prato, 2004), solubility enhancers (Gupta et al, 2006) and for various biotech applications . (Tomalia et al) 2.…”

Section: Introductionmentioning

confidence: 99%