New-generation Jeffamine® D230 core amine, TRIS and carboxylterminated PAMAM dendrimers: Synthesis, characterization and the solubility application for a model NSAID drug Ibuprofen

Abstract

Many therapeutically active drugs are poor water soluble and, therefore, bioavailability of these molecules in the living cells is low and a major problem. In this study, new-generation Jeffamine ® D230 core, amine (NH 2 ), Tris(hydroxymethyl) aminomethane (TRIS), and carboxyl (COOH) terminated poly(amidoamine) PAMAM dendrimers (PAMAMs) were synthesized. Synthesized new-generation PAMAMs were characterized by 1 H NMR, 13 C NMR, ATR-FTIR, and investigated as solubility enhancer of a sample non-steroidal anti-inflammatory drug (NSAID) Ibuprofen (IBU). The effect of generation size (D2-D4), concentration (0-2.0 mM), and surface functional group (NH 2 , COOH, TRIS) of the synthesized new-generation PAMAMs on the aqueous solubility of IBU was also investigated. The observed solubility enhancement of IBU was in the order of D4.COOH (18.21 mg/mL)> D3.COOH (13.21 mg/mL)> D4.TRIS (10.30 mg/mL)> D2.COOH (8.55 mg/mL)> D3.TRIS (6.04 mg/mL)> D4.NH 2 (4.56 mg/mL)> D3.NH 2 (3.36 mg/mL)> D2.TRIS (2.42 mg/mL)> D2.NH 2 (1.86 mg/mL). Results showed that synthesized PAMAMs improved the solubility of IBU significantly (30 to 247-fold) with an increasing generation size, and concentration.

Design of polymer-based antimicrobial hydrogels through physico-chemical transition

“…For example, Javan and coworkers [41] introduced a jeffamine chemical functionalization in hyaluronic acid-based hydrogels to formulate a prolonged and sustained drug release and reduce the number of hydrogel injections: in vivo studies showed the efficiency of this material thanks to the improved biocompatibility and no signal of cell viability reduction. Similar biocompatibility aims were achieved in other works: the jeffamine was used as monomer to preserve some physico-mechanical properties, blood compatibility and cargo release [42][43][44][45], as copolymer with acrylamides derivatives to design 3D scaffolds able to modulate the lower critical solution temperature (LCST) and internalize cells [46] or as cross-linker to satisfy the no-cytotoxicity criteria [47]. However, the evaluation of the polymer antimicrobial features and the design of a 3D scaffold able to preserve them is not widely investigated.…”

Yeni Jenerasyon TREN ve Jeffamine® D230 Çekirdekli PEG Sonlu PAMAM Dendrimerler: Sentezi, Karakterizasyonu, Sulfametoksazol (SMZ) İçin Kompleks ve İn Vitro Salımı Çalışması

“…Son çalışmamızda TREN (T) ve Jeffamine® D230 (D) çekirdekli yüksek jenerasyonlu PAMAM türü dendrimer sentezini ve karakterizasyonu gösterildi (Ertürk et al, 2017b;Gürbüz et al, 2017). Bu çalışmada (T) ve (D) çekirdekli ester sonlu PAMAM dendrimerin (D4.5.COOCH 3 ve T4.5.COOCH 3 ) ~ % 10 oranında PEG bisamin ile modifiye edildikten sonra geriye kalan ester grupları hidroliz edilerek çözünürlüğü çok düşük olmasından dolayı, kanın içinde hızlı emilmemesi, plazma proteinleriyle yetersiz ilişkisi ve birçok yan etkisi (ateş, deri döküntüsü, hematolojik bozukluk, vb.)…”

“…SMZ-PAMAM dendrimer kompleksleri önceki çalışmalarımıza göre hazırlandı (Ertürk et al, 2017b(Ertürk et al, , 2017aGürbüz et al, 2017). 1:1 molar oranında SMZ-PAMAM karışımları metanolde çözüldü.…”

“…SMZ karakteristik bantı λ max = 256 nm'dir. SMZ-PAMAM dendrimer kompleksleri oluştuktan sonra bu bantlarda herhangi bir kayma gözlemlenmedi (Ertürk et al, 2017a(Ertürk et al, , 2017bGürbüz et al, 2017).…”

EDA Çekirdekli Amin, TRIS ve Karboksil Sonlu PAMAM Dendrimerleri Kullanarak Ketoprofenin Çözünürlüğünü Geliştirme

“…KETO-PAMAM dendrimer kompleksleri önceki çalışmalarımıza göre hazırlandı [21,25,26]. 1:1 molar oranında KETO-PAMAM karışımları metanol'de çözüldü.…”