38 research outputs found
Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL10-b-PDMS65-b-PVCL10 vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg−1 single dose) of PVCL10-PDMS65-PVCL10 vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research
Multilayer-derived, ultrathin, stimuli-responsive hydrogels
In addition to a well-known capacity of the layer-by-layer (LbL) technique to create multilayers with strongly bound polymer chains, the technique also provides a unique opportunity to fabricate highly swollen, hydrogel-like films and capsules. Layered, ultrathin hydrogel-like membranes can be fabricated using electrostatically assembled or hydrogen-bonded multilayers as template matrices, or using a click chemistry approach. This review describes recent progress in the area, comparing various approaches used for the fabrication of these surface-mediated, LbL-templated structures, and discusses future applications of ultrathin hydrogel materials
Controlling Mechanical Properties of Poly(methacrylic acid) Multilayer Hydrogels via Hydrogel Internal Architecture
Hydrogel materials are crucial in many applications due
to their
versatility and ability to mimic biological tissues. While manipulating
bulk hydrogel cross-link density, polymer content, chemical composition,
and microporosity has been a main approach to controlling hydrogel
rigidity, altering the internal organization of hydrogel materials
through chain intermixing and stratification can bring finer control
over hydrogel properties, including mechanical responses. We report
on altering the mechanical properties of ultrathin poly(methacrylic
acid) (PMAA) multilayer hydrogels by controlling the internal organization
of the PMAA network. PMAA multilayer hydrogels were synthesized by
cross-linking PMAA layers in poly(N-vinylpyrrolidone)
(PVPON)/PMAA hydrogen-bonded multilayer templates prepared by dipped
or spin-assisted (SA) layer-by-layer assembly using sacrificial PVPON
interlayers with molecular weights of 40,000 or 280,000 g mol–1. The effect of PVPON molecular weight on PMAA hydrogel
stratification and network swelling and hydration was assessed by in situ spectroscopic ellipsometry and neutron reflectometry
(NR). In a new NR modeling of polymer intermixing, we have inferred
nanoscopic structure and water distribution within the ultrathin-layered
films from measured continuum neutron scattering length density (SLD)
and related those to the mechanical properties of the hydrogel films.
We have found that hydrogel swelling, the number of water molecules
associated with the swollen hydrogel, and water density within the
SA PMAA hydrogels can be controlled by choosing low- or high-Mw PVPON. While cross-link densities determined
by ATR-FTIR were similar, greater swelling and hydration at pH >
5
were observed for SA PMAA hydrogels synthesized using higher-Mw PVPON. The enhanced swelling of these SA hydrogels
resulted in softening with a lower Young’s modulus at pH >
5 as measured by colloidal probe atomic force microscopy (AFM). The
effect of PMAA layer intermixing on hydrogel mechanical properties
was also compared for dipped and SA (PMAA) multilayer hydrogels of
similar thickness and cross-linking degree. Despite similar values
of gigapascal-range Young’s modulus for dry PMAA multilayer
hydrogel films, an almost twice greater softening of the SA (PMAA)
hydrogel compared to that prepared by dipping was observed, with Young’s
modulus values decreasing to tens of megapascals in solution at pH
> 5. Our study demonstrates that, unlike simply changing bulk hydrogel
cross-link density, programming polymer network architecture via controlling
the nanostructured organization of SA PMAA hydrogels enables selective
modulation of the cross-link density within hydrogel strata. Control
of polymer chain intermixing through hydrogel stratification offers
a framework for synthesizing materials with finely tuned hydrogel
internal structures, enabling precise control of such physical properties
as the internal architecture, hydrogel swelling, surface morphology,
and mechanical response, which are critical for the application of
these materials in sensing, drug delivery, and tissue engineering
Temperature-Responsive Nanogel Multilayers Of Poly(N-Vinylcaprolactam) For Topical Drug Delivery
We report nanothin temperature-responsive hydrogel films of poly(N-vinylcaprolactam) nanoparticles (νPVCL) with remarkably high loading capacity for topical drug delivery. Highly swollen (νPVCL) n multilayer hydrogels, where n denotes the number of nanoparticle layers, are produced by layer-by-layer hydrogen-bonded assembly of core-shell PVCL-co-acrylic acid nanoparticles with linear PVPON followed by cross-linking of the acrylic acid shell with either ethylene diamine (EDA) or adipic acid dihydrazide (AAD). We demonstrate that a (νPVCL) 5 film undergoes dramatic and reversible swelling up to 9 times its dry thickness at pH = 7.5, indicating 89 v/v % of water inside the network. These hydrogels exhibit highly reversible ∼3-fold thickness changes with temperature variations from 25 to 50 °C at pH = 5, the average pH of human skin. We also show that a (νPVCL) 30 hydrogel loaded with ∼120 µg cm −2 sodium diclofenac, a non-steroidal anti-inflammatory drug used for osteoarthritis pain management, provides sustained permeation of this drug through an artificial skin membrane for up to 24 h at 32 °C (the average human skin surface temperature). The cumulative amount of diclofenac transported at 32 °C from the (νPVCL) 30 hydrogel after 24 h is 12 times higher than that from the (νPVCL) 30 hydrogel at 22 °C. Finally, we demonstrate that the (νPVCL) hydrogels can be used for multiple drug delivery by inclusion of Nile red, fluorescein and DAPI dyes within the νPVCL nanoparticles prior to hydrogel assembly. Using confocal microscopy we observed the presence of separate dye-loaded νPVCL compartments within the hydrogel matrix with all three dyes confined to the nanogel particles without intermixing between the dyes. Our study provides opportunity for development of temperature-responsive multilayer hydrogel coatings made via the assembly of core-shell nanogel particles which can be used for skin-sensitive materials for topical drug delivery
Controlling Internal Organization of Multilayer Poly(methacrylic acid) Hydrogels with Polymer Molecular Weight
We report on tailoring the internal
architecture of multilayer-derived
polyÂ(methacrylic acid) (PMAA) hydrogels by controlling the molecular
weight of polyÂ(<i>N</i>-vinylpyrrolidone) (PVPON) in hydrogen-bonded
(PMAA/PVPON) layer-by-layer precursor films. The hydrogels are produced
by cross-linking PMAA in the spin-assisted multilayers followed by
PVPON release. We found that the thickness, morphology, and architecture
of hydrogen-bonded films and the corresponding hydrogels are significantly
affected by PVPON chain length. For all systems, an increase in PVPON
molecular weight from <i>M</i><sub>w</sub> = 2.5 to 1300
kDa resulted in increased total film thickness. We also show that
increasing polymer <i>M</i><sub>w</sub> smooths the hydrogen-bonded
film surfaces but roughens those of the hydrogels. Using deuterated <i>d</i>PMAA marker layers in neutron reflectometry measurements,
we found that hydrogen-bonded films reveal a high degree of stratification
which is preserved in the cross-linked films. We observed <i>d</i>PMAA to be distributed more widely in the hydrogen-bonded
films prepared with small <i>M</i><sub>w</sub> PVPON due
to the greater mobility of short-chain PVPON. These variations in
the distribution of PMAA are erased after cross-linking, resulting
in a distribution of <i>d</i>PMAA over about two bilayers
for all <i>M</i><sub>w</sub> but being somewhat more widely
distributed in the films templated with higher <i>M</i><sub>w</sub> PVPON. Our results yield new insights into controlling the
organization of nanostructured polymer networks using polymer molecular
weight and open opportunities for fabrication of thin films with well-organized
architecture and controllable function
Architecture of Hydrated Multilayer Poly(methacrylic acid) Hydrogels: The Effect of Solution pH
We report on the evolution of the internal structure of dry and hydrated poly(methacrylic acid) (PMAA) hydrogels by quantifying the extent of layer interdiffusion in hydrogen-bonded (HB) films and upon subsequent cross-linking and hydration. These hydrogels are produced by ethylenediamine (EDA)-assisted cross-linking of PMAA in spin-assisted (SA) and dipped HB PMAA/poly(N-vinylpyrrolidone) (PVPON) multilayers followed by complete release of PVPON at pH 8 due to severing of hydrogen bonds with the PMAA network. Internal hydrogel architecture was monitored by neutron reflectometry using deuterated dPMAA marker layers. We found that even in the highly stratified SA HB films, layer interdiffusion extends over three (PMAA/PVPON) bilayers. Cross-linking of this film induces marker layer interpenetration more deeply into the surrounding material, extending over five layers. The volume fraction of dPMAA at the nominal center of a marker layer decreased from 0.65 to 0.51 after cross-linking. Hydrated SA hydrogels preserve well-organized layering and exhibit a persistent differential swelling with two distinct swelling ratios corresponding to MAA cross-link-rich and cross-link-poor strata. In contrast, layer organization in dipped films decays rapidly with distance from the silicon substrate. Both types of hydrogel swelled by factors of two and four times their dry total thicknesses at pH 5 and 7, respectively, and exhibited elevated surface roughness upon hydration. To fit the neutron reflectometry data, a self-consistent model was developed wherein the amount of PMAA initially deposited was preserved through subsequent chemical modification and hydration. Our results open opportunities for the development of thin hydrogels with a regulated structure, which can be utilized for efficient sensing, protection, activation, and rapid response in an aqueous environment. The internal morphological hierarchy of these multilayer hydrogels affords a means of fine-tuning their response to pH, temperature, or light to a degree rarely possible for randomly cross-linked responsive networks or brushes