###### Abstract  
A series of amphiphilic arborescent copolymers of generations G1 and G2 with an arborescent poly(\(\gamma\)-benzyl L-glutamate) (PBG) core and poly(ethylene oxide) (PEO) chain segments in the shell, PBG-\(g\)-PEO, were synthesized and evaluated as drug delivery nanocarriers. The PBG building blocks were generated by ring-opening polymerization of \(\gamma\)-benzyl L-glutamic acid \(N\)-carboxyanhydride (Glu-NCA) initiated with \(n\)-hexylamine. Partial or full deprotection of the benzyl ester groups followed by coupling with PBG chains yielded a comb-branched (arborescent polymer generation zero or G0) PBG structure. Additional cycles of deprotection and grafting provided G1 and G2 arborescent polypeptides. Side chains of poly(ethylene oxide) were then randomly grafted onto the arborescent PBG substrates to produce amphiphilic arborescent copolymers. Control over the branching density of G0 PBG was investigated by varying the length and the deprotection level of the linear PBG substrates used in their synthesis. Three G0 PBG cores with different branching densities, varying from a compact and dense to a loose and more porous structure, were thus synthesized. These amphiphilic copolymers behaved similar to unimolecular micelles in aqueous solutions, with a unimodal number- and volume-weighted size distributions in dynamic light scattering measurements. It was demonstrated that these biocompatible copolymers can encapsulate hydrophobic drugs such as doxorubicin (DOX) within their hydrophobic core with drug loading efficiencies of 42-65%. Sustained and pH-responsive DOX release was observed from the unimolecular micelles, which suggests that they could be useful as drug nanocarriers for cancer therapy. doxorubicin; arborescent poly(benzyl L-glutamate); drug delivery; sustained release Article Unimolecular Micelles from Randomly Grafted Arborescent Copolymers with Different Core Branching Densities: Encapsulation of Doxorubicin and In Vitro Release Analysis  
[PERSON], [PERSON], [PERSON], M.  
tive of their concentration or the solvency conditions [9; 12; 13; 14; 15; 16; 17]. Due to these remarkable features, the past decade has witnessed a surge of interest in the synthesis and characterization of unimolecular micelles, particularly in relation to biomedical applications. To date, the polymers most widely investigated to form unimolecular micelles for various applications are dendrimers and hyperbranched polymers. Unfortunately, dendrimers are time-consuming and tedious to synthesize, while hyperbranched polymers are easier to synthesize but only with limited control over their structure [18; 19; 20]. In contrast to dendrimers and hyperbranched polymers, dendrigraft (arborescent) polymers are a subset of dendritic polymers derived from reactive polymer building blocks in successive grafting reactions rather than small molecule monomers [21; 22]. Due to the presence of a large number of coupling sites distributed randomly on the grafting substrates, a rapid increase in molecular weight is observed over successive arborescent polymer generations and high molecular weight species are obtained in a few steps, while narrow molecular weight distributions (M\({}_{w}\)/M\({}_{n}\) < 1.1) are maintained in most cases [23]. The ability of nanocarriers to accumulate in target tissues depends on their physicochemical characteristics, among which the particle size is critical. The formulation of safe, stable, and efficient drug delivery systems, with well-defined and predictable release characteristics, requires nanocarriers with a uniform (close to monodisperse) size population [24]. Arborescent unimolecular micelles can be obtained by the addition of hydrophilic segments in the last grafting cycle. For example, arborescent polystyrene-_graft_-poly(2-vinylpyridine) (PS-_g_-P2 VP) copolymers were synthesized by grafting poly(2-vinylpyridine) side chains onto arborescent PS substrates of different generations.