Synthesis and characterization of polylactide‐PAMAM “Janus‐type” linear‐dendritic hybrids

Abstract

Herein, we present a facile and comprehensive synthetic methodology for the preparation of polyester‐polyamidoamine (PAMAM) (i.e., polyester: polylactide [PLA] (hydrophobic) and polyamidoamine, PAMAM [hydrophilic]) polymers. A library of PLA‐PAMAM linear dendritic block copolymers (LDBCs) in which both l and d, l polylactide were employed in mass ratios of 30:70, 50:50, 70:30, and 90:10 (PLA:PAMAM) were synthesized and analyzed. When placed in aqueous media, the immiscibility of the hydrophilic and hydrophobic segments leads to nanophase‐segregation exhibited as the formation of aggregates (e.g., vesicles, worms, and/or micelles). By employing both stereochemical configurations of PLA, the differentiation in mass ratios of PLA‐PAMAM aided in elucidating the structure–property relationships of the LDBC system and provided a means toward the control of nanoparticle morphology. Transmission electron microscopy and dynamic light scattering afford the size and shape of the nanoparticles with diameters ranging from 10.6 for low mass ratios to 122.4 nm for high mass ratios of PLA‐PAMAM and positive zeta‐potential values between +24.7 mV and +48.2 mV. Furthermore, small‐angle X‐ray scattering (SAXS) studies were employed to obtain more detailed information on the morphological assemblies constructed via direct dissolution. Such insights provide a pathway toward nanomaterials with unique morphologies and tunable properties deemed relevant in the development of next generation biomaterials. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1448–1459

Structural and Surface Properties of Polyamidoamine (PAMAM) – Fatty Acid‐based Nanoaggregates Derived from Self‐assembling Janus Dendrimers

“…A general synthetic scheme for the PAMAM‐FA amphiphilic JDs, FA‐PAMAM‐NH 3 + , FA‐PAMAM‐COO − , FA‐PAMAM‐OH, and their precursors, FA‐PAMAM‐BOC, FA‐PAMAM‐TBE, FA‐PAMAM‐THP, is shown in Scheme 1. In our previous work, [32] we observed that amphiphilic block copolymers with 70 : 30 hydrophobic to hydrophilic ratio self‐assemble into bilayer vesicles in water. Based on our observations as well as those of polymer physics, [32,39,40] the molar mass of JDs was designed to keep 70 : 30 hydrophobic to hydrophilic weight ratio between the dendrons to yield more biologically relevant nanoaggregates [41] …”

“…GPC of protected JDs confirmed the absence of free dendrons that had not reacted during the CuAAC process by having a single peak in the chromatographs. Shoulders appearing adjacent to the main peak in the GPC trace are due to the branching nature of the dendrimer affecting its elution in the column (Figures S37–39) [32] . The dispersity values range from 1.02–1.06, which indicates the presence of monodisperse polymers.…”

“…The PAMAM portion was a logical choice for the hydrophilic segment due to its extensive use in drug delivery and biomaterials [31] . The PAMAM structure consists of repeating amide segments, which increases biocompatibility and provides structural gaps to store smaller species via hydrogen bond interactions [18,32] . As the hydrophilic portion, various modifications can be made to the amine terminal groups to yield surface functionalized nanoaggregates in aqueous media.…”

“…[31] The PAMAM structure consists of repeating amide segments, which increases biocompatibility and provides structural gaps to store smaller species via hydrogen bond interactions. [18,32] As the hydrophilic portion, various modifications can be made to the amine terminal groups to yield surface functionalized nanoaggregates in aqueous media. For this investigation, we selected generation-3 (G3) PAMAM.…”

“…Shoulders appearing adjacent to the main peak in the GPC trace are due to the branching nature of the dendrimer affecting its elution in the column ( Figures S37-39). [32] The dispersity values range from 1.02-1.06, which indicates the presence of monodisperse polymers. With the precursors confirmed, acid deprotection affords cationic, anionic (i.e., in buffer), and neutral amphiphilic JDs FA-PAMAM-NH 3 + , FA-PAMAM-COOH, and FA-PAMAM-OH.…”