Electrochemically Enhanced Delivery of Pemetrexed from Electroactive Hydrogels

Abstract

Electroactive hydrogels based on derivatives of polyethyleneglycol (PEG), chitosan and polypyrrole were prepared via a combination of photopolymerization and oxidative chemical polymerization, and optionally doped with anions (e.g., lignin, drugs, etc.). The products were analyzed with a variety of techniques, including: FT-IR, UV-Vis, 1H NMR (solution state), 13C NMR (solid state), XRD, TGA, SEM, swelling ratios and rheology. The conductive gels swell ca. 8 times less than the non-conductive gels due to the presence of the interpenetrating network (IPN) of polypyrrole and lignin. A rheological study showed that the non-conductive gels are soft (G′ 0.35 kPa, G″ 0.02 kPa) with properties analogous to brain tissue, whereas the conductive gels are significantly stronger (G′ 30 kPa, G″ 19 kPa) analogous to breast tissue due to the presence of the IPN of polypyrrole and lignin. The potential of these biomaterials to be used for biomedical applications was validated in vitro by cell culture studies (assessing adhesion and proliferation of fibroblasts) and drug delivery studies (electrochemically loading the FDA-approved chemotherapeutic pemetrexed and measuring passive and stimulated release); indeed, the application of electrical stimulus enhanced the release of PEM from gels by ca. 10–15% relative to the passive release control experiment for each application of electrical stimulation over a short period analogous to the duration of stimulation applied for electrochemotherapy. It is foreseeable that such materials could be integrated in electrochemotherapeutic medical devices, e.g., electrode arrays or plates currently used in the clinic.

Creating 3D Objects with Integrated Electronics via Multiphoton Fabrication In Vitro and In Vivo

“…[ 7,76–78 ] However, PDMS contains ether/organosilicon bonds which may be hepatotoxic/nephrotoxic, [ 79–81 ] it may degrade, [ 82,83 ] and its surface chemistry may need to be tuned to minimize biofouling; [ 84–86 ] pyrrole (acknowledged in supplier's safety data sheets (SDSs), which are of variable quality, to display a degree of toxicity, with significant variation in LD50 between species and mode of administration), the photoinitiator (irgacure D‐2959; SDSs indicating it to be somewhat toxic), and PPY (non‐hazardous in supplier's SDSs), which were predicted to be non‐sensitizers of skin, and non‐mutagenic. [ 73,87 ] Here we screen the other components utilized in the printing of PPY‐based structures within PDMS (employing ink formulations composed of mixtures of the monomer pyrrole, PY; the photoinitiator (irgacure D‐2959), dopant (camphorsulfonic acid, CSA; SDSs indicating it to be corrosive and toxic), and a combination of polyethylene glycol (PEG, 10 kDa; SDSs indicating it to be non‐hazardous) and polyethylene glycol dimethyacrylate (PEGDMA, 2 kDa; SDSs variable, often indicated to be an eye irritant, skin sensitizer, and toxic), depicted in Figure ). In silico toxicity screening studies of the ink components (CSA, and PEG, Table S1, Supporting Information) using Derek Nexus (Derek Nexus: 6.0.1, Nexus: 2.2.2) predicted them to be non‐sensitizers of skin, and in silico mutagenicity screening studies using Sarah Nexus (Sarah Nexus: 3.0.0, Sarah Model: 2.0) predicted them to be non‐mutagenic; by contrast, PEGDMA is predicted to plausibly cause chromosome damage, cause irritation of eyes/skin, be a sensitizer of skin (albeit non‐mutagenic).…”

“…[7,[76][77][78] However, PDMS contains ether/organosilicon bonds which may be hepatotoxic/ nephrotoxic, [79][80][81] it may degrade, [82,83] and its surface chemistry may need to be tuned to minimize biofouling; [84][85][86] pyrrole (acknowledged in supplier's safety data sheets (SDSs), which are of variable quality, to display a degree of toxicity, with significant variation in LD50 between species and mode of administration), the photoinitiator (irgacure D-2959; SDSs indicating it to be somewhat toxic), and PPY (non-hazardous in supplier's SDSs), which were predicted to be non-sensitizers of skin, and non-mutagenic. [73,87] Here we screen the other components utilized in the printing of PPY-based structures within PDMS (employing ink formulations composed of mixtures of the monomer pyrrole, PY; the photoinitiator (irgacure D-2959), dopant (camphorsulfonic acid, CSA; SDSs indicating it to be corrosive and toxic), and a combination of polyethylene glycol (PEG, 10 kDa; SDSs indicating it to be non-hazardous) and polyethylene glycol dimethyacrylate (PEGDMA, 2 kDa; SDSs variable, often indicated to be an eye irritant, skin sensitizer, and toxic), depicted in Figure 1). In silico toxicity screening studies of the ink components (CSA, and PEG, Table S1, Supporting Information) using Derek Nexus (Derek Nexus: 6.0.1, Nexus: 2.2.2) predicted them to be non-sensitizers of skin, and in silico mutagenicity screening studies using Sarah Nexus (Sarah Nexus: 3.0.0, Sarah Model: 2.0) predicted them to be non-mutagenic; by contrast, PEGDMA is predicted to plausibly cause chromosome damage, cause irritation of eyes/skin, be a sensitizer of skin (albeit non-mutagenic).…”

4D Printing: The Development of Responsive Materials Using 3D-Printing Technology

“…These findings highlight the importance and opportunities of post-printing treatments [ 240 ]. In addition, the application of electrical stimulus can be used to enhance the release of drugs [ 241 , 242 ]. A 4D-printed hydrogel based on agarose/alginate–aniline tetramer with the capability of tailored electrically controlled dexamethasone release for neurodegenerative diseases’ treatment.…”

Tuning conductivity while maintaining mechanical properties in perylene bisimide hydrogels at physiological pH

“…8,9 There are many options for achieving conductive materials from the assembly of low-molecular-weight gelators that can be functionalised for specific applications. [10][11][12] The problem lies in the method of gelation, as gelation triggers being often unsuitable for biological applications or resulting in gels with unsuitable properties for physiological conditions. Gels triggered to form at low pH or by applying a solvent switching method that uses toxic solvents would be unsuitable for this application.…”