Diisopropylamino Ethyl Methacrylate Research Articles

Hydrogels with dual sensitivity to temperature and pH in physiologically relevant ranges as supports for versatile controlled cell detachment

Thermosensitive hydrogels based on the N-vinyl caprolactam (VCL), capable of allowing for cell adhesion and proliferation, as well as non-aggressive detachment by controlled temperature drop, were functionalized with 23 % or lower molar percentages of the cationizable hydrophobic unit 2-(diisopropylamino) ethyl methacrylate (DPAEMA), to obtain networks with dual sensitivity to temperature and pH. The swelling analysis of the systems has shown a transition pK (pKb) close to physiological values, dependent on the temperature of the medium (pKb of 6.6 and 6.9 when the temperature of the medium is above and below the transition temperature VPTT, respectively) and little dependence on the degree of functionalization of DPAEMA. In addition, at temperatures below the transition temperature (VPTT), the systems have shown large swelling variations as a function of the pH (i.e. below and above the pKb), exhibiting greater absorption capacity at pHs below pKb, where the DPAEMA units are cationized. Cytocompatibility and transplant capacity have been evaluated using the C166-GFP endothelial cell line. None of the thermosensitive hydrogels with variable DPAEMA content showed a delay with respect to the control without DPAEMA neither in terms of adhesion nor in proliferation. However, by increasing the percentage of DPAEMA functionalization -and decreasing thermosensitivity-, a correlative decrease in mitochondrial activity was obtained in the transplant, with significant differences for the hydrogels with DPAEMA molar percentage of 3 % or higher. Taking advantage of the proximity of the pKb to the physiological value, we have evaluated the cellular response and the capacity for transplantation after lowering the pH to 6.5, below pKb. A direct relationship of the DPAEMA functionalization degree on the detachment efficiency was observed, since the hydrogels with the highest molar load of DPAEMA showed higher mitochondrial metabolic activity after cell detachment.

Development of Hybrid DSPC:DOPC:P(OEGMA950-DIPAEMA) Nanostructures: The Random Architecture of Polymeric Guest as a Key Design Parameter.

Hybrid nanoparticles have gained a lot of attention due to their advantageous properties and versatility in pharmaceutical applications. In this perspective, the formation of novel systems and the exploration of their characteristics not only from a physicochemical but also from a biophysical perspective could promote the development of new nanoplatforms with well-defined features. In the current work, lipid/copolymer bilayers were formed in different lipid to copolymer ratios and examined via differential scanning calorimetry as a preformulation study to decipher the interactions between the biomaterials, followed by nanostructure preparation by the thin-film hydration method. Physicochemical and toxicological evaluations were conducted utilizing light scattering techniques, fluorescence spectroscopy, and MTS assay. 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in different weight ratios were the chosen lipids, while a linear random copolymer with pH- and thermoresponsive properties comprised of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA) in different ratios was used. According to our results, non-toxic hybrid nanosystems with stimuli-responsive properties were successfully formulated, and the main parameters influencing their overall performance were the hydrophilic/hydrophobic balance, lipid to polymer ratio, and more importantly the random copolymer topology. Hopefully, this investigation can promote a better understanding of the factors affecting the behavior of hybrid systems.

Preparation of polymeric vesicles with tertiary amine and epoxy functional groups via polymerization-induced self-assembly

Polymeric vesicles with tertiary amine and epoxy functional groups were fabricated via the reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and glycidyl methacrylate (GlyMA) in an ethanol-water mixture by using poly (ethylene oxide)-4-(4-Cyanopentanoic acid) dithiobenzoate (mPEG45-CPADB) as the macro-chain-transfer agent (macro-CTA). Biocompatible polymer mPEG45 with molecular weight of 2000 and 4-(4-Cyanopentanoic acid) dithiobenzoate (CPADB) were used for the macro-CTA synthesizing via the esterification reaction. Investigation of the degree of polymerization (DP) of the hydrophobic block P(DIPEMA-co-GlyMA) and the solid content indicated that both have significant effect on the particle morphology and particle diameter. 1H NMR and FTIR analysis indicated the existing of tertiary amine and epoxy functional groups on the produced vesicles.

Preparation of polymeric vesicles via redox-initiated RAFT dispersion polymerization

2-(diisopropylamino) ethyl methacrylate (DIPEMA) and glycidyl methacrylate (GlyMA) were used for the investigation of the redox-initiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization, by using poly (ethylene oxide)-4-(4-Cyanopentanoic acid) dithiobenzoate (mPEG-CPADB) as the macro-chain-transfer agent (macro-CTA). The particle growth process study indicated that the particles changed from spheres to worms, and then to vesicles during the polymerization process. The degree of polymerization (DP) of the hydrophobic block P(DIPEMA-co-GlyMA) affected the particle morphology, particle diameter and molecular weight significantly. Pure polymeric vesicles could be obtained when DP was equal to or higher than 60, and with increasing of the DP of the hydrophobic block, the diameter and the molecular weight of the particles both increased.

Tumor micro-environment sensitive release of doxorubicin through chitosan based polymeric nanoparticles: An in-vitro study

Conventional chemotherapy poses toxic effects to healthy tissues. A therapeutic system is thus required that can administer, distribute, metabolize, and excrete medicine from human body without damaging healthy cells. This is possible by designing a therapeutic system that can release drug at specific target tissue. In current work, novel chitosan (CS) based polymeric nanoparticles (PNPs) containing N-isopropyl acrylamide (NIPAAM) and 2-(di-isopropyl amino) ethyl methacrylate (DPA) are designed. The presence of available functional groups i.e. OH− (3262 cm−1), –NH2 (1542 cm−1), and CO (1642 cm−1), was confirmed by Fourier Transform Infra-red Spectrophotometry (FTIR). The surface morphology and average particle size (175 nm) was determined through Scanning Electron Microscope (SEM). X-Ray Diffractometry (XRD) studies confirmed the amorphous nature and excellent thermal stability of PNPs up to 100 °C with only 2.69% mass loss was confirmed by Thermogravimetric analysis (TGA). The pH sensitivity of such PNPs for release of encapsulated doxorubicin at malignant site was investigated. The encapsulation efficiency of PNPs was 89% (4.45 mg/5 mg) for doxorubicin (a chemotherapeutic) measured by using UV–Vis Spectrophotometer. The drug release profile of loaded PNPs was 88% (3.92 mg/4.45 mg) at pH 5.3, in 96 h. PNPs with varying DPA concentration can effectively be used to deliver chemotherapeutic agents with high efficacy.

Microwave Irradiation-Assisted Reversible Addition-Fragmentation Chain Transfer Polymerization-Induced Self-Assembly of pH-Responsive Diblock Copolymer Nanoparticles.

Herein, we present a versatile platform for the synthesis of pH-responsive poly([N-(2-hydroxypropyl)]methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate] diblock copolymer (PHPMA-b-PDPA) nanoparticles (NPs) obtained via microwave-assisted reversible addition-fragmentation chain transfer polymerization-induced self-assembly (MWI-PISA). The N-(2-hydroxypropyl) methacrylamide (HPMA) monomer was first polymerized to obtain a macrochain transfer agent with polymerization degrees (DPs) of 23 and 51. Subsequently, using mCTA and 2-(diisopropylamino)ethyl methacrylate (DPA) as monomers, we successfully conducted MWI-PISA emulsion polymerization in aqueous solution with a solid content of 10 wt %. The NPs were obtained with high monomer conversion and polymerization rates. The resulting diblock copolymer NPs were analyzed by dynamic light scattering (DLS) and cryogenic-transmission electron microscopy (cryo-TEM). cryo-TEM studies reveal the presence of only NPs with spherical morphology such as micelles and polymer vesicles known as polymersomes. Under the selected conditions, we were able to fine-tune the morphology from micelles to polymersomes, which may attract considerable attention in the drug-delivery field. The capability for drug encapsulation using the obtained in situ pH-responsive NPs, the polymersomes based on PHPMA23-b-PDPA100, and the micelles based on PHPMA51-b-PDPA100 was demonstrated using the hydrophobic agent and fluorescent dye as Nile red (NR). In addition, the NP disassembly in slightly acidic environments enables fast NR release.

Intracellular transport of biomacromolecular drugs by a designed microgel capsule with pH/redox stimulus-responsiveness

Biological macromolecular drugs usually have good efficacy and recognition performance. However, due to their large molecular weight and easy degradation/inactivation, general carriers are difficult to transport them into cell stably and safely. Here, a pH/redox dual-responsive microgel capsule was prepared for constructing a double-locked drug delivery system. Firstly, the pH-sensitive poly(ethyleneimine)-block-poly(2-(diisopropylamino ethylmethacry-late)-block-poly(ethyleneimine) triblock copolymers (PEI-PDPA-PEI) were synthesized for preparing polymer vesicles. The PEI layer was crosslinked by disulfide groups to finally obtain pH/redox dual-responsive microgel capsule, marked as P-VesicleGEL. Then, the P-VesicleGEL was used to encapsulate different types of drugs (doxorubicin hydrochloride, rhodamine, proteins, aptamer), and had a higher loading capacity than the corresponding polymer micelles for macromolecules. Compared with small molecules, P-VesicleGEL had much better "double-locked" function for macromolecules. I.e., only when the two “locks” were opened simultaneously the release could be triggered. Furtherly, cell experiments had proved that the P-VesicleGEL had excellent biocompatibility and cell transfection ability. It could not only effectively identify normal and cancer cells, but also transport biological drugs that were difficult to enter into cells by themselves. The microgel capsule designed here is expected to be applied for the intracellular delivery/release of biological macromolecular drugs.

Interfacial Rearrangements of Block Copolymer Micelles Toward Gelled Liquid-Liquid Interfaces with Adjustable Viscoelasticity.

Though amphiphiles are ubiquitously used for altering interfaces, interfacial reorganization processes are in many cases obscure. For example, adsorption of micelles to liquid-liquid interfaces is often accompanied by rapid reorganizations toward monolayers. Then, the involved time scales are too short to be followed accurately. A block copolymer system, which comprises poly(ethylene oxide)110 -b-poly{[2-(methacryloyloxy)ethyl]diisopropylmethylammonium chloride}170 (i.e., PEO110 -b-qPDPAEMA170 with quaternized poly(diisopropylaminoethyl methacrylate)) is presented. Its reorganization kinetics at the water/n-decane interface is slowed down by electrostatic interactions with ferricyanide ([Fe(CN)6 ]3- ). This deceleration allows an observation of the restructuring of the adsorbed micelles not only by tracing the interfacial pressure, but also by analyzing the interfacial rheology and structure with help of atomic force microscopy. The observed micellar flattening and subsequent merging toward a physically interconnected monolayer lead to a viscoelastic interface well detectable by interfacial shear rheology (ISR). Furthermore, the "gelled" interface is redox-active, enabling a return to purely viscous interfaces and hence a manipulation of the rheological properties by redox reactions. Additionally, interfacial Prussian blue formation stiffens the interface. Such manipulation and in-depth knowledge of the rheology of complex interfaces can be beneficial for the development of emulsion formulations in industry or medicine, where colloidal stability or adapted permeability is crucial.

Co-delivery of doxorubicin and CRISPR/Cas9 or RNAi-expressing plasmid by chitosan-based nanoparticle for cancer therapy

Folic acid (FA) and 2-(Diisopropylamino) ethyl methacrylate (DPA) double grafted trimethyl chitosan (TMC) nanoparticles (FTD NPs) were synthesized for the co-delivery of doxorubicin (DOX) and Survivin CRISPR/Cas9-expressing plasmid (sgSurvivin pDNA) or Survivin shRNA-expressing plasmid (iSur pDNA). FA modification enhanced the uptake of DOX and pDNA loaded into FTD NPs in tumor cells. A rapid release of DOX was triggered under acidic conditions due to pH-sensitiveness of FTD NPs arising from DPA conjugation. Negligible differences between FTD/sgSurvivin pDNA NPs and FTD/iSur pDNA NPs demonstrated that RNA interference (RNAi) and CRISPR/Cas9 technologies possessed comparable antitumor efficiency. Notably, the in vitro and in vivo antitumor efficacies of FTD/DOX/sgSurvivin pDNA NPs were superior to those of single delivery of DOX or sgSurvivin pDNA, while were comparable to those of FTD/DOX/iSur pDNA NPs. These results suggested that the combination of chemotherapeutics and CRISPR/Cas9 systems would provide a potential modality for cancer therapy.

PH and Temperature Double-Switch Hybrid Micelles for Controllable Drug Release.

pH/temperature dual-responsive hybrid micelles were prepared for constructing a double-locked drug delivery system. The temperature-sensitive polyethylene glycol-poly(tetrahydropyranylmethacrylate)-polyethylene glycol (PEG-PTHPMA-PEG) triblock copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization and amide coupling reaction. pH-sensitive poly(2-(diisopropylamino ethylmethacrylate)-polyethylene glycol (PDPA-PEG) diblock polymers were introduced, which could self-assemble with PEG-PTHPMA-PEG in aqueous solutions to form hybrid micelles. The anticancer drug doxorubicin, which was encapsulated in the core of the hybrid micelles, could be released only under simultaneous stimulations of pH and temperature. It was proved that the micelles could maintain their structural stability under a unilateral stimulus, while the structure collapsed and recombined under a double stimulus, which triggered a large amount of drug release. Furthermore, the excellent biocompatibility and dual sensitivity of the vector were also proved by cytotoxicity experiments. The dual-responsive hybrid micelles designed here showed the advantages of a double insurance lock of drug leakage and precise controllability of drug release, which could act as accurate drug delivery systems.

Phase Separation of Aqueous Poly(diisopropylaminoethyl methacrylate) upon Heating.

Poly(diisopropylaminoethyl methacrylate) (PDPA) is a pH- and thermally responsive water-soluble polymer. This study deepens the understanding of its phase separation behavior upon heating. Phase separation upon heating was investigated in salt solutions of varying pH and ionic strength. The effect of the counterion on the phase transition upon heating is clearly demonstrated for chloride-, phosphate-, and citrate-anions. Phase separation did not occur in pure water. The buffer solutions exhibited similar cloud points, but phase separation occurred in different pH ranges and with different mechanisms. The solution behavior of a block copolymer comprising poly(dimethylaminoethyl methacrylate) (PDMAEMA) and PDPA was investigated. Since the PDMAEMA and PDPA blocks phase separate within different pH- and temperature ranges, the block copolymer forms micelle-like structures at high temperature or pH.

Facile construction of beads-on-a-string complexes of polymeric micelles and DNA via tunable electrostatic interactions

Inspired by the structure of chromatin fibers, the compaction of DNA by cationic nanoparticles has received much attention in the fields of nanomaterials and biotechnology. However, the fabrication of artificial chromatin-biomimetic assemblies of DNA and nanoparticles in biological environments is still a challenge due to their dependence on uncontrollable electrostatic interactions. Herein, block and random copolymerization of 2-(diisopropylamino)ethyl methacrylate (DPA) and 2-(dimethylamino)ethyl methacrylate (DMA) were used to regulate the charge density and distribution of cationic polyethylene glycol-b-poly(tertiary amine methacrylate) micelles, adjusting the electrostatic interaction between the micelles and DNA. We showed that the assembled PEG-b-PDMA-b-PDPA micelle/DNA system exhibited a strong electrostatic interactions between the micelles and DNA, causing uncontrollable intrachain flocculation. However, the assembled PEG-b-P(DMA-r-DPA) micelle/DNA system showed relatively week, tunable electrostatic interactions, leading to an open -chromatin-like structure

An acid-triggered porphyrin-based block copolymer for enhanced photodynamic antibacterial efficacy

Bacterial infection, especially multidrug-resistant (MDR) bacterial infection has threatened public health drastically. Here, we fabricate an “acid-triggered” nanoplatform for enhanced photodynamic antibacterial activity by reducing the aggregation of photosensitizers (PSs) in bacterial acidic microenvironment. Specifically, a functional amphiphilic block copolymer was first synthesized by using a pH-sensitive monomer, 2-(diisopropylamino) ethyl methacrylate (DPA) and porphyrin-based methacrylate (TPPC6MA) with poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) as the macromolecular chain transfer agent, and POEGMA-b-[PDPA-co-PTPPC6MA] block copolymer was further self-assembled into spherical nanoparticles (PDPA-TPP). PDPA-TPP nanoparticles possess an effective electrostatic adherence to negatively charged bacterial cell membrane, since they could rapidly achieve positive charge in acidic bacterial media. Meanwhile, the acid-triggered dissociation of PDPA-TPP nanoparticles could reduce the aggregation caused quenching (ACQ) of the photosensitizers, leading to around 5 folds increase of the singlet oxygen (1O2) quantum yield. In vitro results demonstrated that the “acid-triggered” PDPA-TPP nanoparticles could kill most of MDR S. aureus (Gram-positive) and MDR E. coli (Gram-negative) by enhanced photodynamic therapy, and they could resist wound infection and accelerate wound healing effectively in vivo. Furthermore, PDPA-TPP nanoparticles could well disperse the biofilm and almost kill all the biofilm-containing bacteria. Thus, by making use of the bacterial acidic microenvironment, this “acid-triggered” nanoplatform in situ will open a new path to solve the aggregation of photosensitizers for combating broad-spectrum drug-resistant bacterial infection.

Electrochemical Stimulation of Water-Oil Interfaces by Nonionic-Cationic Block Copolymer Systems.

Variable interfacial tension could be desirable for many applications. Beyond classical stimuli like temperature, we introduce an electrochemical approach employing polymers. Hence, aqueous solutions of the nonionic-cationic block copolymer poly(ethylene oxide)114-b-poly{[2-(methacryloyloxy)ethyl]diisopropylmethylammonium chloride}171 (i.e., PEO114-b-PDPAEMA171 with a quaternized poly(diisopropylaminoethyl methacrylate) block) were investigated by emerging drop measurements and dynamic light scattering, analyzing the PEO114-b-qPDPAEMA171 impact on the interfacial tension between water and n-decane and its micellar formation in the aqueous bulk phase. Potassium hexacyanoferrates (HCFs) were used as electroactive complexants for the charged block, which convert the bishydrophilic copolymer into amphiphilic species. Interestingly, ferricyanides ([Fe(CN)6]3-) act as stronger complexants than ferrocyanides ([Fe(CN)6]4-), leading to an insoluble qPDPAEMA block in the presence of ferricyanides. Hence, bulk micellization was demonstrated by light scattering. Due to their addressability, in situ redox experiments were performed to trace the interfacial tension under electrochemical control, directly utilizing a drop shape analyzer. Here, the open-circuit potential (OCP) was changed by electrolysis to vary the ratio between ferricyanides and ferrocyanides in the aqueous solution. While a chemical oxidation/reduction is feasible, also an electrochemical oxidation leads to a significant change in the interfacial tension properties. In contrast, a corresponding electrochemical reduction showed only a slight response after converting ferricyanides to ferrocyanides. Atomic force microscopy (AFM) images of the liquid/liquid interface transferred to a solid substrate showed particles that are in accordance with the diameter from light scattering experiments of the bulk phase. In conclusion, the present results could be an important step toward economic switching of interfaces suitable, e.g., for emulsion breakage.

Surface Modification of Cellulose Nanocrystals via RAFT Polymerization of CO2-Responsive Monomer-Tuning Hydrophobicity.

Cellulose nanocrystals (CNCs) were converted into a CO2-responsive composite nanomaterial by grafting poly(dimethylaminoethyl methacrylate) (PDMAEMA), poly(diethylaminoethyl methacrylate) (PDEAEMA), and poly(diisopropylaminoethyl methacrylate) (PDPAEMA) onto its surface using both grafting-to and grafting-from approaches. The zeta potential (ζ) of the graft-modified CNC could be reversibly switched by protonation/deprotonation of the tertiary amine groups simply by sparging with CO2 and N2, respectively. Depending on the grafting density and the molecular weight of the polymer grafts, CNC can form stable aqueous dispersions at either mildly acidic pH (under CO2) or mildly basic (under N2) conditions. Moreover, it was also determined that the CNC hydrophobicity, assessed using phase-shuttling experiments at different pH values, was also dependent on both the grafting density and molecular weight of the polymer grafts, thereby making it possible to easily tune CNC dispersibility and/or hydrophobicity.

Double security drug delivery system DDS constructed by multi-responsive (pH/redox/US) microgel

In this paper, the multi-responsive core-shell microgels were prepared for constructing a double-locked drug delivery system. The pH- sensitive poly(2-(diisopropylamino ethylmethacry-late)-block-poly(ethyleneimine) diblock copolymers (PDPA-b-PEI) were synthesized and used to prepare micelles through their self-assembly in neutral solution. Redox-responsive gel shells were formed by Michael addition of primary amine group of branched PEI using disulfide as a cross-linker, which was specifically cleaved by glutathione (GSH). Anticancer drug doxorubicin DOX and perfluorohexane (PFH) could be encapsulated in the core of microgel. The DOX was released sustainably only under the condition of pH and GSH were both right. For example, under neutral condition with GSH, DOX could not release swimmingly due to the core of microgels was in hydrophobic state and wrapped the DOX firmly, although the gel shells were collapsed by GSH. When exposed to ultrasound, the drug released abruptly and achieved a complete release instantly. Moreover, it was found that the structure of the microgels was not destroyed after the ultrasound stimulus but had undergone an expansion-recovery process. Finally, it was demonstrated that the microgel had a “double security” effect, ensuring the low drug leakage during the normal blood circulation and efficient drug release under the pH/redox/ultrasound stimulus. The multi-responsive microgels designed here, which combines the usage of both endogenous and exogenous stimuli, has the advantages of low side-effect, high spatiotemporal controllability and complete release.

PH-Responsive benzaldehyde-functionalized PEG-based polymeric nanoparticles for drug delivery: Effect of preparation method on morphology, dye encapsulation and attachment

Functionalized, pH-responsive and biocompatible polymeric nanoparticles have attracted the interest of many researchers working on novel pharmaceutical formulations. Here, in an effort to develop an efficient drug delivery formulation, all these properties are combined in one polymeric nanoparticle system. More specifically, benzaldehyde-functionalized amphiphilic block copolymers based on PEG-based oligo(ethylene glycol) methacrylate (OEGMA), benzaldehyde-containing para-formyl phenyl methacrylate (pFPMA) and pH-responsive 2-(diisopropyl)aminoethyl methacrylate (DPA) monomers are readily prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. pH-Switch and single emulsion-solvent evaporation post-polymerization processing methods are used to prepare benzaldehyde-functionalized PEGylated pH-responsive nanoparticles with diameters of 180–230 nm. After nanoparticle formation, the benzaldehyde groups on the surface are shown to react with an Alexa Fluor 488 hydroxylamine dye through oxime bond formation, illustrating the potential for these particles to be surface-functionalized with biologically important molecules, such as fluorescent dyes for tracking their intracellular fate or antibodies for targeted therapy. Encapsulation of Nile Red and rhodamine 6G dyes is performed during the post-polymerization processing step for nanoparticle formation. Nanoparticles with a fluorescent cargo were shown to be successfully internalized in both A2780 ovarian cancer and A549 lung epithelial human cells in vitro, further illustrating the potential for these formulations to be used as triggered release therapeutic drug delivery vehicles.

Directed Insertion of Light-Activated Proteorhodopsin into Asymmetric Polymersomes from an ABC Block Copolymer.

Nanoscopic artificial vesicles containing functional protein transporters are fundamental for synthetic biology. Energy-providing modules, such as proton pumps, are a basis for simple nanoreactors. We report on the first insertion of a functional transmembrane protein into asymmetric polymersomes from an ABC triblock copolymer. The polymer with the composition poly(ethylene glycol)-poly(diisopropylaminoethyl methacrylate)-poly(styrenesulfonate) (PEG-PDPA-PSS) was synthesized by sequential controlled radical polymerization. PEG and PSS are two distinctively different hydrophilic blocks, allowing for a specific orientation of our protein, the light-activated proton pump proteorhodopsin (PR), into the final proteopolymersome. A very interesting aspect of the PEG-PDPA-PSS triblock copolymers is that it allowed for simultaneous vesicle formation and oriented insertion of PR simply by adjusting the pH. The intrinsic positive charge of PR's intracellular surface was enhanced by a His-tag, which aligns readily with the negative charges of the PSS on the outside of the polymersomes. The directed insertion of PR was confirmed by a light-dependent pH change of the proteopolymersome solution, indicating the intended orientation. We have hereby demonstrated the first successful oriented insertion of a proton pump into an artificial asymmetric membrane.

Polymerization-Induced Self-Assembly Generating Vesicles with Adjustable pH-Responsive Release Performance

Stimuli-responsive polymeric vesicles have attracted great attention in drug delivery due to their intrinsic hollow structures and “on demand” release of drugs upon environmental stimuli. The drug-release kinetics from polymeric vesicles, which is usually dependent on the stimuli-responsive behaviors of the polymeric vesicle, has great impacts on the therapeutic efficacy. Over the past decade, polymerization-induced self-assembly (PISA) has been demonstrated to be a powerful strategy to prepare the polymeric vesicles. However, fabrication of stimuli-responsive vesicles with adjustable drug release kinetics via PISA has been rarely reported, which may be due to the poor selectivity of functional membrane-forming polymers in the PISA system. Herein, a series of vesicles with different pH-responsive behaviors were fabricated via RAFT dispersion copolymerization of (diisopropylamino)ethyl methacrylate (DIPEMA) and benzyl methacrylate (BzMA). Both the content of DIPEMA units in hydrophobic P(DIPEMA-co-BzMA) bl...

Uptake and release of Dexamethasone using pH-responsive poly(2-hydroxyethyl methacrylate-co-2-(diisopropylamino)ethyl methacrylate) hydrogels for potential use in ocular drug delivery

pH-responsive hydrogels prepared by copolymerization between 2-hydroxyethyl methacrylate (HEMA) and 2-(diisopropylamino)ethyl methacrylate (DPA) appear to be a promising system for controlling Dexamethasone 21-disodium phosphate (DXP) release behaviors for ophthalmological treatments. The incorporation and subsequent release of DXP by HEMA-DPA copolymers have been evaluated in different pH mediums and in vitro conditions. Optical and morphological characteristics, as well as wettability, drug-matrix interactions and drug-release properties, were assessed. Drug incorporation was maximum at pH 6.5 and at an initial drug concentration of 200 mg/L. Additionally, increasing the DPA content and cross-linker ratio increased the amount of loaded DXP. The amount of DXP released was approximately 70%, and the entire release process took 20–40 h. Moreover, the copolymers showed changes in the release rate in response to small pH variations (between 7.0 and 7.8). Additionally, DXP release by the copolymers far exceeded the estimated concentration of the drug absorbed in the eyes by drop administration.