Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous solution

Buczkowski, Adam; Olesiński, Tomasz; Zbicinska, Elzbieta; Urbaniak, Paweł; Pałecz, Bartłomiej

doi:10.1016/j.ijpharm.2015.05.033

Cited by 24 publications

(9 citation statements)

References 94 publications

(106 reference statements)

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“…The combination ability of PAMAM with fluorouracil depends on the surface groups and generation of PAMAM. Experiments showed that fluorouracil-loading capacity was higher with cationic PAMAM–NH 2 dendrimer than with the hydroxyl analog PAMAM–OH 26 . There is also a positive correlation between fluorouracil-loading capacity and the generation of PAMAM, which is reasonable because higher generation contains more binding sites 27 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of post-trabeculectomy fibrosis via topically instilled antisense oligonucleotide complexes co-loaded with fluorouracil

Jiang

Chen

Tai

et al. 2020

Acta Pharmaceutica Sinica B

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Trabeculectomy is the mainstay of surgical glaucoma treatment, while the success rate was unsatisfying due to postoperative scarring of the filtering blebs. Clinical countermeasures for scar prevention are intraoperative intervention or repeated subconjunctival injections. Herein, we designed a co-delivery system capable of transporting fluorouracil and anti-TGF- β 2 oligonucleotide to synergistically inhibit fibroblast proliferation via topical instillation. This co-delivery system was built based on a cationic dendrimer core (PAMAM), which encapsulated fluorouracil within hydrophobic cavity and condensed oligonucleotide with surface amino groups, and was further modified with hyaluronic acid and cell-penetrating peptide penetratin. The co-delivery system was self-assembled into nanoscale complexes with increased cellular uptake and enabled efficient inhibition on proliferation of fibroblast cells. In vivo studies on rabbit trabeculectomy models further confirmed the anti-fibrosis efficiency of the complexes, which prolonged survival time of filtering blebs and maintained their height and extent during wound healing process, exhibiting an equivalent effect on scar prevention compared to intraoperative infiltration with fluorouracil. Qualitative observation by immunohistochemistry staining and quantitative analysis by Western blotting both suggested that TGF- β 2 expression was inhibited by the co-delivery complexes. Our study provided a potential approach promising to guarantee success rate of trabeculectomy and prolong survival time of filtering blebs.

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Section: Discussionmentioning

confidence: 99%

Inhibition of post-trabeculectomy fibrosis via topically instilled antisense oligonucleotide complexes co-loaded with fluorouracil

Jiang

Chen

Tai

et al. 2020

Acta Pharmaceutica Sinica B

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“…Small molecular-weight drugs such as 5-FU, which are loosely entrapped in the DH network, are expected to diffuse out freely through the interconnected pores, causing a burst drug release. However, those 5-FU molecules entrapped within dendrimers via electrostatic and hydrophobic interaction may be released at a much slower rate. , Through these two release mechanisms, DH is expected to provide a sufficient initial release of 5-FU and a more sustained release afterward to maintain a high drug concentration at the tumor site after local injection, compared to the free 5-FU. However, the DH/5-FU formulation needs to be optimized depending on demand.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery

Cooper

Wang

et al. 2017

ACS Biomater. Sci. Eng.

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We developed novel dendrimer hydrogels (DH)s on the basis of bioorthogonal chemistry, in which polyamidoamine (PAMAM) dendrimer generation 4.0 (G4) functionalized with strained alkyne dibenzocyclooctyne (DBCO) via PEG spacer (Mn = 2,000 g/mol) underwent strain-promoted azide-alkyne cycloaddition (SPAAC) with polyethylene glycol bisazide (PEG-BA) (Mn= 20,000 g/mol) to generate a dendrimer-PEG cross-linked network. This platform offers a high degree of functionality and modularity. A wide range of structural parameters including dendrimer generation, degree of PEGylation, loading density of clickable DBCO groups, PEG-BA chain length as well as the ratio of clickable dendrimer to PEG-BA and their concentrations can be readily manipulated to tune chemical and physical properties of DHs. We used this platform to prepare an injectable liquid DH. This bioorthogonal DH exhibited high cytocompatibility and enabled sustained release of the anticancer drug 5-fluorouracil (5-FU). Following intratumoral injection, the DH/5-FU formulation significantly suppressed tumor growth and improved survival of HN12 tumor-bearing mice by promoting tumor cell death as well as by reducing tumor cell proliferation and angiogenesis.

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“…The terminal/surface groups further have an effect on the solubilization of PAMAM dendrimer. The effects of hydroxyl and amine terminated PAMAM dendrimer generation 5 (PAMAM-NH2 and PAMAM-OH) on increasing solubility, equilibrium dialysis, and loading of an antitumor drug 5-fluorouracil (5-FU, 10 ) have been investigated [ 40 ]. PAMAM-NH2 showed higher incorporation of a 5-FU drug by three times compared to PAMAM-OH terminated dendrimer, whereby 70% and 14% of 5-FU ( 10 ) drugs were incorporated into PAMAM-NH2 and PAMAM-OH, respectively.…”

Section: Experimental Insights On Pamam-drug Interactions For Enhamentioning

confidence: 99%

“…PAMAM-NH2 showed higher incorporation of a 5-FU drug by three times compared to PAMAM-OH terminated dendrimer, whereby 70% and 14% of 5-FU ( 10 ) drugs were incorporated into PAMAM-NH2 and PAMAM-OH, respectively. The decrease of entropy (S < 0) favored higher incorporation of the drug into PAMAM-NH2 than for PAMAM-OH demonstrating high entropy (S > 0) of the system [ 40 ]. Furthermore, PAMAM-NH2 increased the solubility of 5-FU three times compared to PAMAM-OH.…”

Section: Experimental Insights On Pamam-drug Interactions For Enhamentioning

confidence: 99%

“…Furthermore, PAMAM-NH2 increased the solubility of 5-FU three times compared to PAMAM-OH. In addition, it was observed that weakly acidic drugs like 5-FU bind weakly to hydroxyl terminated PAMAM dendrimers, as 5-FU cannot protonate the hydroxyl groups of PAMAM-OH unlike PAMAM-NH2 [ 40 ]. Despite the high solubility and incorporation effects that PAMAM-NH2 has over PAMAM-OH on 5-FU, the former is still challenged by toxicity [ 54 ].…”

Section: Experimental Insights On Pamam-drug Interactions For Enhamentioning

confidence: 99%

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Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies

et al. 2018

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Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment.

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Spectroscopic and calorimetric studies of formation of the supramolecular complexes of PAMAM G5-NH2 and G5-OH dendrimers with 5-fluorouracil in aqueous solution

Cited by 24 publications

References 94 publications

Inhibition of post-trabeculectomy fibrosis via topically instilled antisense oligonucleotide complexes co-loaded with fluorouracil

Inhibition of post-trabeculectomy fibrosis via topically instilled antisense oligonucleotide complexes co-loaded with fluorouracil

Synthesis and Application of Injectable Bioorthogonal Dendrimer Hydrogels for Local Drug Delivery

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies

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