Here, we demonstrate the applicability of self‐assembling linear‐dendritic block copolymers (LDBCs) and their nanoaggregates possessing varied surfaces as therapeutic nanocarriers. These LDBCs are comprised of a hydrophobic, linear polyester chemically coupled to a hydrophilic dendron polyamidoamine (PAMAM)—the latter of which acts as the surface of the self‐assembled nanoaggregate in aqueous media. To better understand how surface charge density affects the overall operability of these nanomaterials, we modified the nanoaggregate surface to yield cationic (NH3+), neutral (OH), and anionic (COO−) surfaces. The effect of these modifications on the physicochemical properties (i.e., size, morphology, and surface charge density), colloidal stability, and cellular uptake mechanism of the polymeric nanocarrier were investigated. This comparative study demonstrates the viability of nanoaggregates formed from PDLLA‐PAMAM LDBCs to serve as nanocarriers for applications in drug delivery.
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
- NSF-PAR ID:
- 10461105
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Polymer Science Part A: Polymer Chemistry
- Volume:
- 57
- Issue:
- 13
- ISSN:
- 0887-624X
- Page Range / eLocation ID:
- p. 1448-1459
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
more » « less
ABSTRACT Carbohydrates are the fundamental building blocks of many natural polymers, their wide bioavailability, high chemical functionality, and stereochemical diversity make them attractive starting materials for the development of new synthetic polymers. In this work, one such carbohydrate,
d ‐glucopyranoside, was utilized to produce a hydrophobic five‐membered cyclic carbonate monomer to afford sugar‐based amphiphilic copolymers and block copolymers via organocatalyzed ring‐opening polymerizations with 4‐methylbenzyl alcohol and methoxy poly(ethylene glycol) as initiator and macroinitiator, respectively. To modulate the amphiphilicities of these polymers acidic benzylidene cleavage reactions were performed to deprotect the sugar repeat units and present hydrophilic hydroxyl side chain groups. Assembly of the polymers under aqueous conditions revealed interesting morphological differences, based on the polymer molar mass and repeat unit composition. The initial polymers, prior to the removal of the benzylidenes, underwent a morphological change from micelles to vesicles as the sugar block length was increased, causing a decrease in the hydrophilic–hydrophobic ratio. Deprotection of the sugar block increased the hydrophilicity and gave micellar morphologies. This tunable polymeric platform holds promise for the production of advanced materials for implementation in a diverse range of applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2019 ,57 , 432–440 -
more » « less
ABSTRACT Glycohydrogels containing 2′‐acrylamidoethyl‐β‐
d ‐galactopyranoside and varying levels ofN ,N ′ methylene bisacrylamide and 3‐acrylamidopropyltris(trimethylsiloxy)silane were synthesized to determine the effects of crosslinker and amphipathic balance on equilibrium water content (EWC), bound water population, and hydrogen bonding dynamics at the water–polymer interface. Analogous dimethylacrylamide hydrogels were synthesized for comparison with a system containing lower hydrogen bonding propensity. An approach combining experiment (proton nuclear magnetic resonance, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption analysis) and molecular dynamics simulations was employed to examine the relationship between bulk hydrogel properties, molecular water mobility, and hydrogen bonding characteristics. It was found that copolymer composition (hydrophobic content) and crosslink concentration in high water content glycohydrogels affect EWC, and by extension, structural water population. The organization of water at the polymer interface is greatly impacted by the surrounding environment, where hindered molecular water mobility promotes water–polymer binding and decreases water–water clustering. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2019 ,57 , 584–597 -
more » « less
Background Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin‐azithromycin sinus stent (CASS) in vitro.
Methods The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly‐
l ‐lactic acid (PLLA) stent. In‐vitro evaluation included: (1) assessment of drug‐coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti‐biofilm activities againstPseudomonas aeruginosa .Results The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reduced
P aeruginosa biofilm mass compared with bare stents and controls (relative optical density units at 590‐nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000;p < 0.001; n = 3).Conclusion The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti‐biofilm activities against
P aeruginosa . Further studies evaluating the efficacy of CASS in a preclinical model are planned. -
Chain orientation, a natural consequence of polymer film processing, often leads to enhanced mechanical properties parallel to the machine extrusion direction (MD), while leaving the properties in the transverse direction (TD) unaffected or diminished, as compared to the unoriented material. Here, we report that mixing poly(ethylene oxide)-block-poly(butylene oxide) (PEO-PBO) diblock copolymer that forms dispersed particles in an amorphous polylactide (PLA) matrix produces uniaxially stretched blend films with enhanced toughness in both the MD and TD. Small-angle X-ray scattering experiments and visual observations revealed that the dominant deformation mechanism for blend films transitions from crazing to shear yielding in the MD as the stretching ratio increases, while crazing is the primary deformation mechanism in the TD at all stretching ratios investigated. As the films age at room temperature, crazing becomes more prevalent in the MD without compromising the improved toughness. The stretched blend films were susceptible to some degree of mechanical aging in the TD but remained fivefold tougher than stretched neat PLA films for up to 150 days. This work presents a feasible route to produce uniaxially stretched PEO–PBO/PLA films that are mechanically tough, which provides a more sustainable plastic alternative.more » « less
