Claw Amphiphiles with a Dendrimer Core: Nanoparticle Stability and Drug Encapsulation Are Directly Proportional to the Number of Digits

There are numerous pharmaceutical, food, and consumer product applications requiring the incorporation of hydrophobic solutes within aqueous media. Often amphiphiles and/or polymers are used to produce encapsulating nanostructures. Because the encapsulation efficiencies of these nanostructures directly impact on the process or product, it is often desirable to optimize this parameter. To produce these advanced functional materials, we hypothesized that an amphiphile with a claw shape would favor polymer aggregation into nanoparticles and hydrophobic compound encapsulation. Claw amphiphiles were prepared by attaching one end of comb-shaped chitosan amphiphile chains [N,N,N-trimethyl, N,N-dimethyl, N-monomethyl, N-palmitoyl, N-acetyl, 6-O-glycol chitosan (GCPQA)] to a central dendrimer core [generation 3 diaminobutane poly(propylenimine) dendrimer (DAB)] to give DAB-GCPQA. The linear chitosan amphiphile (GCPQA) forms the digits of the claw. These claw amphiphiles were very stable and had a high encapsulating efficiency. DAB-GCPQAs (Mn = 30 and 70 kDa) had extremely low critical micelle concentrations [CMCs = 0.43 μg mL–1 (13 nM) and 0.093 μg mL–1 (0.9 nM), respectively], and their CMCs were lower than that of linear GCPQA [Mn = 14 kDa, CMC = 0.77 μg mL–1 (38 nM)]. The claw amphiphile CMCs decreased linearly with the number of digits (r2 = 0.98), and drug encapsulation (hydrophobic drug propofol) in 4 mg mL–1 dispersions of the amphiphiles increased linearly (r2 = 0.94) with the number of digits. DAB-GCPQA70 (4 mg mL–1, 0.058 mM) encapsulated propofol (7.3 mg mL–1, 40 mM). Finally, despite their stability, claw amphiphile nanoparticles are able to release the encapsulated drug in vivo, as shown with the claw amphiphile–propofol formulations in a murine loss of righting reflex model.