Chemo-Enzymatic Synthesis of Perfluoroalkyl-Functionalized Dendronized Polymers as Cyto-Compatible Nanocarriers for Drug Delivery Applications

Abstract

Among amphiphilic polymers with diverse skeletons, fluorinated architectures have attracted significant attention due to their unique property of segregation and self-assembly into discrete supramolecular entities. Herein, we have synthesized amphiphilic copolymers by grafting hydrophobic alkyl/perfluoroalkyl chains and hydrophilic polyglycerol [G2.0] dendrons onto a co-polymer scaffold, which itself was prepared by enzymatic polymerization of poly[ethylene glycol bis(carboxymethyl) ether]diethylester and 2-azidopropan-1,3-diol. The resulting fluorinated polymers and their alkyl chain analogs were then compared in terms of their supramolecular aggregation behavior, solubilization capacity, transport potential, and release profile using curcumin and dexamethasone drugs. The study of the release profile of encapsulated curcumin incubated with/without a hydrolase enzyme Candida antarctica lipase (CAL-B) suggested that the drug is better stabilized in perfluoroalkyl chain grafted polymeric nanostructures in the absence of enzyme for up to 12 days as compared to its alkyl chain analogs. Although both the fluorinated as well as non-fluorinated systems showed up to 90% release of curcumin in 12 days when incubated with lipase, a comparatively faster release was observed in the fluorinated polymers. Cell viability of HeLa cells up to 95% in aqueous solution of fluorinated polymers (100 µg/mL) demonstrated their excellent cyto-compatibility.

Fabrication of nanostructures through self-assembly of non-ionic amphiphiles for biomedical applications

“…It has been observed that the formulation of curcumin/amphiphile in 1 : 5 ratio (w/w) led the C-18 alkyl containing amphiphile 22 to encapsulate higher percentage of curcumin as compared to the C-18 alkyl functionalized PEGylated copolymers employing 1 : 2 curcumin/polymer ratio (Table 4). 48 Moreover, the synthesized amphiphiles 20-22 using 1 : 5 and 1 : 2 formulation ratio were found to possess superior transport efficiency, transport capacity and % encapsulation efficiency as compared to the alkyl and peruoroalkyl-functionalized dendronized polymers synthesized earlier by our group, 58 wherein 1 : 3 curcumin/polymer ratio was used (Table 4). Furthermore, Rabanel et al 59 also used 1 : 5 loading ratio for PEGpoly lactic acid (PLA) polymers (PEG 8%-g-PLA, PEG 20%-g-PLA, PEG-b-PLA and OH-g-PLA) but reported lower % transport and encapsulation efficiency than our system, with the exception of PEG 8%-g-PLA (Table 4).…”

“…6). This 48 1 : 2 --15.41 Stearoyl polymer 48 1 : 2 --9.26 50% peruoroalkyl-functionalized dendronized polymers 58 1 : 3 0.53 213.17 1.6 70% peruoroalkyl-functionalized dendronized polymers 58 1 : 3 0.45 176.75 1.4 50% alkyl-functionalized dendronized polymers 58 1 : 3 0.27 98.95 0.8 70% alkyl-functionalized dendronized polymers 58 1 : 3 0.39 135.41 1.2 PEG-PLA polymer 59 1 : 5 <2 -</¼ 10 PEG 8%-g-PLA polymer 59 1 : 5 5 -15 mPEG 2000 -OA polymer 60 1 : 5 $6 -$20…”

“…Moreover, higher dexamethasone carrying ability of the synthesized nanocarriers 20-22 was observed on comparison with those of peruoroalkyl-functionalized dendronized polymers reported earlier by our group. 58 It was of interest to note the correlation between the CAC of a nanotransporter with its dye/drug loading capacity; in fact, amphiphile 22 allowed to encapsulate approximately 1.6-6 times more dye/drug, in most cases, than the nanocarrier 21. Nevertheless, it was possible to conrm the fundamental importance of the hydrophobicity of the micellar core from the results collected, that allowed the formation of relatively larger aggregates (amphiphile 22), and ultimately enabling high dye/ drug solubilization.…”

Fabrication of oligo‐glycerol based hydrolase responsive amphiphilic nanocarriers

“…As a part of our ongoing research program to synthesize a wide variety of amphiphilic nanocarrier systems capable of forming different morphological aggregates because of varied hydrophilic and hydrophobic segments, herein, we have used triglycerol, an oligomer of glycerol, as a backbone.…”

Synthesis and Characterization of Poly(1,4,7-Trioxacycloundecane-8,11-dione) Macrocyclic Functionalized Hydrogel for High Selectivity Adsorption and Complexation of Bismuth Ion

“…Host-guest adsorption exploits characteristic morphological properties of substrates to separate and adsorb only the substrates which can fit into the macrocyclic cavities. This phenomenon was adopted from biological macrocyclic chelators [13,14] and supramolecular chemistry [15][16][17]. Attempts to translate this mechanism onto adsorbents have not been very successful, with few exceptions (e.g., the SuperLig ® adsorbent) [18][19][20].…”