An official website of the United States government
Abstract Non‐spherical stimuli‐responsive polymeric particles have shown critical importance in therapeutic delivery. Herein, pH‐responsive poly(methacrylic acid) (PMAA) cubic hydrogel microparticles are synthesized by crosslinking PMAA layers within PMAA/poly(N‐vinylpyrrolidone) hydrogen‐bonded multilayers templated on porous inorganic microparticles. This study investigates the effects of template porosity and surface morphology on the PMAA multilayer hydrogel microcube properties. It is found that the hydrogel structure depends on the template's calcination time and temperature. The pH‐triggered PMAA hydrogel cube swelling depends on the hydrogel's internal architecture, either hollow capsule‐like or non‐hollow continuous hydrogels. The loading efficiency of the doxorubicin (DOX) drug inside the microcubes is analyzed by high‐performance liquid chromatography (HPLC), and shows the dependenceof the drug uptake on the network structure and morphology controlled by the template porosity. Varying the template calcination from low (300 °C) to high (1000 °C) temperature results in a 2.5‐fold greater DOX encapsulation by the hydrogel cubes. The effects of hydrogel surface charge on the DOX loading and release are also studied using zeta‐potential measurements. This work provides insight into the effect of structural composition, network morphology, and pH‐induced swelling of the cubical hydrogels and may advance the development of stimuli‐responsive vehicles for targeted anticancer drug delivery.
more »
« less
Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules
Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.
more »
« less
- Award ID(s):
- 1754078
- PAR ID:
- 10124518
- Date Published:
- Journal Name:
- Polymers
- Volume:
- 10
- Issue:
- 12
- ISSN:
- 2073-4360
- Page Range / eLocation ID:
- 1342
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Despite the potential use of polyelectrolyte multilayers for biomedical, separation, and energy applications, their dynamic properties are not sufficiently understood. In this work, center-of-mass diffusion of a weak polyacid—poly(methacrylic acid) (PMAA) of linear and 8-arm architecture (L-PMAA and 8-PMAA, respectively) and matched molecular weight—was studied in layer-by-layer (LbL) assemblies with poly(diallyldimethylammonium) chloride (PDADMAC) of varied molecular weight. The film deposition at low-salt, acidic conditions when PMAA was only partially ionized yielded thicker, more diffused layers with shorter PDADMAC chains, and bilayer thickness decreased for multilayers constructed with longer PDADMAC. The molecular architecture of PMAA had a weak effect on film growth, with bilayer thickness being ∼20% larger for L-PMAA for the films constructed with the shortest PDADMAC (35 kDa) and identical film growth for L-PMAA and 8-PMAA with the longest PDADMAC (300 kDa). The exposure of the multilayer films to 0.2M NaCl triggered a reduction in PMAA ionization and significant lateral diffusivity of fluorescently labeled PMAA molecules (PMAA*), with diffusion coefficients D ranging from 10−13 to 10−12 cm2/s, as determined by the fluorescence recovery after photobleaching technique. For all the films, polymer mobility was higher for star polyacids as compared to their linear counterparts, and the dependence of PMAA diffusion coefficient D on PDADMAC molecular weight (D ∼ M−n) was relatively weak (n < 0.6). However, 8-PMAA demonstrated an approximately doubled power exponent compared to the L-PMAA chains, suggesting a stronger effect of the molecular connectivity of the partner polycation molecules on the diffusion of star polyelectrolytes.more » « less
-
null (Ed.)Droplet-based microfluidics is used to fabricate thin shell hydrogel microcapsules for the removal of methylene blue (MB) from aqueous solutions. The microcapsules composed of a poly(methacrylic acid) hydrogel shell exhibit unique properties, including permeation, separation, purification, and reaction of molecular species. Photocatalytic TiO 2 and ZnO nanoparticles encapsulated in the microcapsules, i.e. photocatalyst in capsule (PIC), are used to remove organic pollutants using an adsorption–oxidation mechanism. A prototype flow microreactor is assembled to demonstrate a controllable water purification approach in short time using photocatalysts. Our studies of aqueous and homogeneous hydrogel environments for the photocatalysts provide important insights into understanding the effectiveness of MB removal. Hydrogel capsules have MB removal rate comparable to homogeneous particles. Further reduction of both capsule and photocatalyst sizes can potentially aid in quicker water purification.more » « less
-
Abstract We developed the dynamic assembly of the hydrogen‐bonded multilayers of (poly(N‐vinylpyrrolidone/poly(methacrylic acid)) (PVPON/PMAA)) and compared their properties to the static multilayers. We found that dynamic multilayers, wherein a planar substrate is shaken during polymer adsorption, leads to a 15‐time faster deposition of the planar coatings. The thicknesses and roughness of the dynamic coatings were found to be ⁓30% larger than those of static (no shaking) multilayer films as measured by spectroscopic ellipsometry and atomic force microscopy. We examined the film growth, mechanical properties, wettability, hydration, and pH stability of the planar static and dynamic multilayers and demonstrated that these properties were insignificantly affected by the assembly mode. Both static and dynamic coatings produced microporous films when exposed to pH = 5.9, close to the film critical dissolution pH = 6. We discovered that during the release of the multilayer films into a solution to produce free‐standing films either as planar membranes or multilayer capsule shells, the molecular chain rearrangements result in the decreased roughness for both static and dynamic multilayers and lead to a decreased thickness of the dynamic multilayers. Our findings can help develop a rapid synthesis of thicker nanostructured polymer coatings for sensing and controlled delivery applications.more » « less
-
null (Ed.)Polymeric vehicles that efficiently package and controllably release nucleic acids enable the development of safer and more efficacious strategies in genetic and polynucleotide therapies. Developing delivery platforms that endogenously monitor the molecular interactions, which facilitate binding and release of nucleic acids in cells, would aid in the rational design of more effective vectors for clinical applications. Here, we report the facile synthesis of a copolymer containing quinine and 2-hydroxyethyl acrylate that effectively compacts plasmid DNA (pDNA) through electrostatic binding and intercalation. This polymer system poly(quinine- co -HEA) packages pDNA and shows exceptional cellular internalization, transgene expression, and low cytotoxicity compared to commercial controls for several human cell lines, including HeLa, HEK 293T, K562, and keratinocytes (N/TERTs). Using quinine as an endogenous reporter for pDNA intercalation, Raman imaging revealed that proteins inside cells facilitate the unpackaging of polymer–DNA complexes (polyplexes) and the release of their cargo. Our work showcases the ability of this quinine copolymer reporter to not only facilitate effective gene delivery but also enable diagnostic monitoring of polymer–pDNA binding interactions on the molecular scale via Raman imaging. The use of Raman chemical imaging in the field of gene delivery yields unprecedented insight into the unpackaging behavior of polyplexes in cells and provides a methodology to assess and design more efficient delivery vehicles for gene-based therapies.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/polym10121342
