###### Abstract  
A thermosensitive copolymer composed of amphiphilic triblock copolymer, poloxamer 407, grafted on hydrophilic pullulan with pendant carboxymethyl groups (CMP) was prepared and characterized. The structure of the new copolymer was assessed by Fourier transform infrared (FT-IR) and \({}^{1}\)H nuclear magnetic resonance (\({}^{1}\)H NMR) spectroscopy. The content of the poloxamer in the grafted copolymer was 83.8% (\(\
u/w\)). The effect of the copolymer concentration on the gelation behavior was analyzed by the vertical method and rheological tests; the gel phase of the copolymer occurred at a lower concentration (11%, \(w/v\)) as compared with poloxamer (18%, \(v/v\)). The starting gelation time under the simulated physiological conditions (phosphate buffer with a pH of 7.4, at 37 \({}^{\circ}\)C) was sensitive on the rest temperature before the test, this being 990 s and 280 s after 24 h rest at 4 \({}^{\circ}\)C and 20 \({}^{\circ}\)C, respectively. The rheological tests evidenced a high elasticity and excellent ability of the copolymer to recover the initial structure after the removal of the applied force or external stimuli. Moreover, the hydrogel has proved a sustained release of amoxicillin (taken as a model drug) over 168 h. Taken together, the results clearly indicate that this copolymer can be used as an injectable hydrogel. pulululan; poloxamer 407; injectable copolymer; sol-gel transition; drug delivery system 2021  
13 July 2021  
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as oral solutions, suspensions, inhalation formulations, intravenous (IV), ophthalmic or topical formulations [8; 9]. It was found that injected Pluronic in rats is eliminated in a great measure within 3 days, especially by renal excretion and also, to a smaller extent, by biliary excretion [10]. Other studies demonstrated that doses up to 8.75 mL of 22% Pluronic F127 can be administrated to a 70 kg person without inducing hyperlipidemia or altering other blood values [11]. The concentrated aqueous solutions of poloxamer 407 become a thermoreversible gel, which makes this copolymer an interesting formulation choice for optimizing drug formulations and drug administration applications [12; 13; 14]. The transition temperature of poloxamer 407 from aqueous solution to gel (Tsol-gel) depends on the polymer concentration and increases with decreasing the poloxamer concentration. Below a critical concentration threshold, poloxamer no longer gels due to the low number of hydrophobic interactions between polymer chains [7]. Furthermore, the addition of pharmaceually active ingredients, salts, excipients and other compounds to poloxamer 407-based formulations may increase or decrease the Tsol-gel [15; 16]. The grafting of synthetic polymers on natural polysaccharides has been widely used as one of the most convenient ways to combine the advantages of natural and synthetic macromolecules, particularly in applications in which the interactions are desired to manipulate biological responses, such as growth factor binding or enzymatic degradation. [17]. The nonhydrolytically degradable block polymers are often conjugated to natural molecules to impart points of local hydrolytic or enzymatic degradation [18; 19; 20]. Compared to poloxamer copolymers, grafted copolymers can form reversible gels with significant elastic modulus in water at a lower concentration above a certain temperature. Recent studies have reported the synthesis and evaluation of poloxamer 407-grafted copolymers, i.e., poly(acrylic acid) [21; 22; 23; 24], oligo(lactic acid) [25], chondro 6-sulfate [26], heparin [27; 28], alginate [29; 30; 31], chitosan [32; 33] and hyaluronic acid [34] as efficient vehicles for protein, vaccine and drug delivery using in situ formation property. Most of these gels were stable against degradation for a least 20-30 days. Poloxamer 407-grafted chitosan showed improved aqueous stability and biocompatibility, which was due to the polysaccharide moiety [33].