Photoresponse of new azo pyridine functionalized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate).

A new azo polymer containing photoisomerizable azo pyridine functionalities was synthesized via Mitsunobu reaction of 4-(4-hydroxyphenylazo)pyridine with poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) for creating new photochromic materials. The resulting polymer with azo pyridine side groups was characterized for structural, thermal, and optical properties. UV-vis, 1H NMR and IR spectroscopies confirmed that all hydroxyl groups in p(HEMA-co-MMA) were substituted with azo dye. The obtained azo copolymer exhibited high thermal stability (around 240 °C) and a glass transition temperature (113 °C), promising for applications. The trans-to-cis isomerization upon UV irradiation and the thermal back reaction of the azo chromophore in the copolymer in the solid state was studied. A photostationary state with 50% content of cis-isomers upon 6 min of UV irradiation was reached, and during 48 h dark relaxation at ambient temperature, all cis-isomers converted to the trans form. Additionally, the possibility of efficient photogeneration of surface relief gratings with high amplitude of azo copolymer surface modulation was demonstrated.

Piperacillin/Tazobactam Co-Delivery by Micellar Ionic Conjugate Systems Carrying Pharmaceutical Anions and Encapsulated Drug.

Previously obtained amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA) ionic liquid were used as the matrices of three types of nanocarriers, i.e., conjugates with ionic piperacillin (PIP) and micelles with tazobactam (TAZ), which represented single systems, and dual systems bearing PIP anions and encapsulated TAZ for co-delivery. The exchange of Cl anions in TMAMA units with PIP ones resulted in a yield of 45.6-72.7 mol.%. The self-assembling properties were confirmed by the critical micelle concentration (CMC), which, after ion exchange, increased significantly (from 0.011-0.020 mg/mL to 0.041-0.073 mg/mL). The amphiphilic properties were beneficial for TAZ encapsulation to reach drug loading contents (DLCs) in the ranges of 37.2-69.5 mol.% and 50.4-80.4 mol.% and to form particles with sizes of 97-319 nm and 24-192 nm in the single and dual systems, respectively. In vitro studies indicated that the ionically conjugated drug (PIP) was released in quantities of 66-81% (7.8-15.0 µg/mL) from single-drug systems and 21-25% (2.6-3.9 µg/mL) from dual-drug systems. The release of encapsulated TAZ was more efficient, achieving 47-98% (7.5-9.0 µg/mL) release from the single systems and 47-69% (9.6-10.4 µg/mL) release from the dual ones. Basic cytotoxicity studies showed non-toxicity of the polymer matrices, while the introduction of the selected drugs induced cytotoxicity against normal human bronchial epithelial cells (BEAS-2B) with the increase in concentration.

Ionic Liquid-Based Polymer Matrices for Single and Dual Drug Delivery: Impact of Structural Topology on Characteristics and In Vitro Delivery Efficiency.

Previously reported amphiphilic linear and graft copolymers, derived from the ionic liquid [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA_Cl‾), along with their conjugates obtained through modification either before or after polymerization with p-aminosalicylate anions (TMAMA_PAS‾), were employed as matrices in drug delivery systems (DDSs). Based on the counterion type in TMAMA units, they were categorized into single drug systems, manifesting as ionic polymers with chloride counterions and loaded isoniazid (ISO), and dual drug systems, featuring ISO loaded in self-assembled PAS conjugates. The amphiphilic nature of these copolymers was substantiated through the determination of the critical micelle concentration (CMC), revealing an increase in values post-ion exchange (from 0.011-0.063 mg/mL to 0.027-0.181 mg/mL). The self-assembling properties were favorable for ISO encapsulation, with drug loading content (DLC) ranging between 15 and 85% in both single and dual systems. In vitro studies indicated ISO release percentages between 16 and 61% and PAS release percentages between 20 and 98%. Basic cytotoxicity assessments using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) test affirmed the non-toxicity of the studied systems toward human non-tumorigenic lung epithelial cell line (BEAS-2B) cell lines, particularly in the case of dual systems bearing both ISO and PAS simultaneously. These results confirmed the effectiveness of polymeric carriers in drug delivery, demonstrating their potential for co-delivery in combination therapy.

Characterization of Graft Copolymers Synthesized from p-Aminosalicylate Functionalized Monomeric Choline Ionic Liquid.

An ionic liquid based on the monomeric choline, specifically [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (TMAMA), underwent biofunctionalization through an ion exchange reaction with the model drug anion: p-aminosalicylate (PAS), a primary antibiotic for tuberculosis treatment. This modified biocompatible IL monomer (TMAMA/PAS) was subsequently copolymerized with methyl methacrylate (MMA) to directly synthesize the well-defined graft conjugates with regulated content of ionic fraction with PAS anions (up to 49%), acting as drug delivery systems. The length of the polymeric side chains was assessed by the monomer conversions, yielding a degree of polymerization ranging from 12 to 89. The density of side chains was controlled by "grafting from" using the multifunctional macroinitiators. In vitro drug release, triggered by the ion exchange between the pharmaceutical and phosphate anions in a PBS medium, occurred in the range of 71-100% (2.8-9.8 µg/mL). Owing to significant drug content and consistent release profiles, these particular graft copolymers, derived from biomodified IL monomers with ionically attached pharmaceutical PAS in the side chains, are recognized as potentially effective drug delivery vehicles.

Self-Assembling Polymers with p-Aminosalicylate Anions Supported by Encapsulation of p-Aminosalicylate for the Improvement of Drug Content and Release Efficiency.

Bioactive linear choline-based copolymers were developed as micellar carriers for drug delivery systems (DDSs). The polymethacrylates containing trimethylammonium groups with p-aminosalicylate anions (PAS-based copolymers: series 1) or chloride anions (Cl-based copolymers: series 2) differing in ionic content and chain length were selected for drug loading. The diverse structures of amphiphilic copolymers made it possible to adjust the encapsulation efficiency of a well-known antibiotic, i.e., p-aminosalicylate in the form of sodium salt (PASNa) or acid (PASA), providing single drug systems. Goniometry was applied to verify the self-assembly capacity of the copolymers using the critical micelle concentration (CMC = 0.03-0.18 mg/mL) and the hydrophilicity level quantifying the surface wettability of polymer film using the water contact angle (WCA = 30-53°). Both parameters were regulated by the copolymer composition, indicating that the increase in ionic content caused higher CMC and lower WCA, but the latter was also modified to a less hydrophilic surface by drug encapsulation. The drug content (DC) in the PAS-based polymers was increased twice by encapsulation of PASNa and PASA (47-96% and 86-104%), whereas in the chloride-based polymer systems, the drug was loaded in 43-96% and 73-100%, respectively. Efficient drug release was detected for PASNa (80-100% series 1; 50-100% series 2) and PASA as complete in both series. The strategy of loading extra drug by encapsulation, which enhances the drug content in the copolymers containing anions of the same pharmaceutics, provided promising characteristics, which highlight the potential of PAS-loaded micellar copolymers for drug delivery.

Toxicity evaluation of choline ionic liquid-based nanocarriers of pharmaceutical agents for lung treatment.

In vitro cytotoxicity evaluation of linear copolymer (LC) containing choline ionic liquid units and its conjugates with an antibacterial drug in anionic form, that is, p-aminosalicylate (LC_PAS), clavulanate (LC_CLV), or piperacillin (LC_PIP) was carried out. These systems were tested against normal: human bronchial epithelial cells (BEAS-2B), and cancers: adenocarcinoma human alveolar basal epithelial cells (A549), and human non-small cell lung carcinoma cell line (H1299). Cells viability, after linear copolymer LC and their conjugates addition for 72 h, was measured at concentration range of 3.125-100 µg/mL. The MTT test allowed the designation of IC50 index, which was higher for BEAS-2B, and significantly lower in the case of cancer cell lines. The cytometric analyzes, that is, Annexin-V FITC apoptosis assay and cell cycle analysis as well as gene expression measurements for interleukins IL6 and IL8 were carried out, and showed pro-inflammatory activity of tested compounds toward cancer cells, while it was not observed against normal cell line.

Synthesis and Characterization of Linear Copolymers Based on Pharmaceutically Functionalized Monomeric Choline Ionic Liquid for Delivery of p-Aminosalicylate.

Bioactive linear poly(ionic liquid)s (PIL) were designed as carriers in drug delivery systems (DDS). Their synthesis was based on a monomeric ionic liquid (MIL) with a relevant pharmaceutical anion to create therapeutically functionalized monomers, which further can be used in the controlled atom transfer radical polymerization (ATRP). The presence of chloride counterions in the quaternary ammonium groups of choline MIL, e.g., [2-(methacryloyloxy)ethyl]trimethyl-ammonium chloride (ChMACl), was stimulated to undergo the anion exchange with p-aminosalicylate sodium salt (NaPAS) as the source of the pharmaceutical anion with antibacterial activity. The resultant [2-(methacryloyloxy)ethyl]trimethylammonium p-aminosalicylate (ChMAPAS) was copolymerized to attain the well-defined linear choline-based copolymers with various contents of PAS anions (24-42%), which were regulated by the initial ratio of ChMAPAS to MMA and conversion degree. The length of polymeric chains was evaluated by the total monomer conversion (31-66%) yielding degree of polymerization (DPn = 133-272). Depending on the polymer carrier composition, PAS anions were exchanged by 60-100% within 1 h, 80-100% within 4 h, and completely after 24 h by phosphate anions in PBS imitating a physiological fluid.

Eco-Conscious Approach to Thermoresponsive Star-Comb and Mikto-Arm Polymers via Enzymatically Assisted Atom Transfer Radical Polymerization Followed by Ring-Opening Polymerization.

This study explores the synthesis, characterization, and application of a heterofunctional initiator derived from 2-hydroxypropyl cyclodextrin (HP-ß-CD), having eight bromoester groups and thirteen hydroxyl groups allowing the synthesis of mikto-arm star-shaped polymers. The bromoesterification of HP-ß-CD was achieved using α-bromoisobutyryl bromide as the acylation reagent, modifying the cyclodextrin (CD) molecule as confirmed by electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy analysis, and differential scanning calorimetry (DSC) thermograms. The initiator's effectiveness was further demonstrated by obtaining star-comb and mikto-arm polymers via an enzymatically assisted atom transfer radical polymerization (ATRP) method and subsequent ring-opening polymerization (ROP). The ATR polymerization quality and control depended on the type of monomer and was optimized by the way of introducing the initiator into the reaction mixture. In the case of ATRP, high conversion rates for poly(ethylene oxide) methyl ether methacrylate (OEOMA), with molecular weights (Mn) of 500 g/mol and 300 g/mol, were achieved. The molecular weight distribution of the obtained polymers remained in the range of 1.23-1.75. The obtained star-comb polymers were characterized by different arm lengths. Unreacted hydroxyl groups in the core of exemplary star-comb polymers were utilized in the ROP of ε-caprolactone (CL) to obtain a hydrophilic mikto-arm polymer. Cloud point temperature (TCP) values of the synthesized polymers increased with arm length, indicating the polymers' reduced hydrophobicity and enhanced solvation by water. Atomic force microscopy (AFM) analysis revealed the ability of the star-comb polymers to create fractals. The study elucidates advancements in the synthesis and utilization of hydrophilic sugar-based initiators for enzymatically assisted ATRP in an aqueous solution for obtaining complex star-comb polymers in a controlled manner.

Pharmaceutical Functionalization of Monomeric Ionic Liquid for the Preparation of Ionic Graft Polymer Conjugates.

Polymerizable choline-based ionic liquid (IL), i.e., [2-(methacryloyloxy)ethyl]-trimethylammonium (TMAMA/Cl¯), was functionalized by an ion exchange reaction with pharmaceutical anions, i.e., cloxacillin (CLX¯) and fusidate (FUS¯), as the antibacterial agents. The modified biocompatible IL monomers (TMAMA/CLX¯, TMAMA/FUS¯) were copolymerized with methyl methacrylate (MMA) to prepare the graft copolymers (19-50 mol% of TMAMA units) serving as the drug (co)delivery systems. The in vitro drug release, which was driven by the exchange reaction of the pharmaceutical anions to phosphate ones in PBS medium, was observed for 44% of CLX¯ (2.7 µg/mL) and 53% of FUS¯ (3.6 µg/mL) in the single systems. Similar amounts of released drugs were detected for the dual system, i.e., 41% of CLX¯ (2.2 µg/mL) and 33% of FUS¯ (2.0 µg/mL). The investigated drug ionic polymer conjugates were examined for their cytotoxicity by MTT test, showing a low toxic effect against human bronchial epithelial cells (BEAS-2B) and normal human dermal fibroblasts (NHDF) as the normal cell lines. The satisfactory drug contents and the release profiles attained for the well-defined graft polymers with ionically bonded pharmaceuticals in the side chains make them promising drug carriers in both separate and combined drug delivery systems.

Stimuli-Responsive Star Polymer as an Admixture for Crystallization of Hollow Crystals.

Polymers are becoming a very popular tool in the crystallization of different compounds. In this work, a new method of crystallization is proposed using stimuli-responsive star polymer in order to obtain hollow structure crystals. In these experiments, amphiphilic copolymer of acrylic acid (AA) and methyl acrylate (MA) were used for isohydric crystallization via they cooling of KCl in deionized water solution. The experiments were realized in quartz cuvette with a magnetic stirrer using a specialized spectrometer with precise temperature control. The crystallization course was monitored by the absorbance readings and analysis of the nucleation energetic effect. It was proved that the moment of the polymer's phase transition occurrence had an important role in the crystal growth process. On the other hand, the occurrence of phase transition did not trigger the nucleation. The supercoolings achieved in the presence of the polymer were significantly higher compared to pure salt crystallization. On the basis of analysis of Particle Size Distribution (PSD) and Critical Aggregation Concentration (CAC) of the polymer, it was proposed that the hydrophobic particles of macromolecules created from polymeric aggregates served as templates for the formation of hollow crystals. Their purity was verified using thermogravimetric analysis (TGA), 1H NMR, and XRD. Only trace amounts of polymer were found in the crystalline product.

Rhodamine-Tagged Polymethacrylate Dyes as Alternative Tools for Analysis of Plant Cells.

A rhodamine B (RhB)-based initiator for atom transfer radical polymerization (ATRP) was synthesized and applied for preparation of poly(2-trimethylammoniumethyl methacrylate) (PChMA), poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(2-trimethylsilyloxyethyl methacrylate) (PHEMATMS). Polymer fluorescence was confirmed by determination of quantum yield by comparative method with piroxicam as the standard exhibiting dependency of emission intensity on the polymer chain hydrophilicity and the kind of solvent. The RhB functionalized polymers were used for biological tests in plant materials except for RhB-PHEMATMS because of weak fluorescence. These two polymers slightly differed in cellular localization. RhB-PChMA was mostly observed in cell walls of root tissues and cotyledon epidermis. It was also observed in cytoplasm and cell organelles of root cap cells and rhizodermis, in contrast with cytoplasm of cotyledon epidermis. RhB-PHEMA was also present in apoplast. A strong signal in protoxylem cell walls and a weak signal in cell walls of rhizodermis and cortex were visible. Moreover, it was also present in cell walls of cotyledon epidermis. However, RhB-PHEMA was mostly observed in cytoplasm and cell organelles of all root tissues and epidermis of cotyledons. Both RhB-polymers did not cause cell death which means that they can be used in living plant material.

Dual-Drug Delivery via the Self-Assembled Conjugates of Choline-Functionalized Graft Copolymers.

Graft copolymers based on a choline ionic liquid (IL), [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (TMAMA), were obtained by atom transfer radical polymerization. The presence of chloride counterions in the trimethylammonium groups promoted anion exchange to introduce fusidate anions (FUS, 32−55 mol.%) as the pharmaceutical anions. Both the choline-based IL copolymers and their ionic drug-carrier conjugates (FUS systems as the first type, 26−208 nm) formed micellar structures (CMC = 0.011−0.025 mg/mL). The amphiphilic systems were advantageous for the encapsulation of rifampicin (RIF, 40−67 mol.%), a well-known antibiotic, resulting in single-drug (RIF systems as the second type, 40−95 nm) and dual-drug systems (FUS/RIF as the third type, 31−65 nm). The obtained systems released significant amounts of drugs (FUS > RIF), which could be adjusted by the content of ionic units and the length of the copolymer side chains. The dual-drug systems released 31−55% FUS (4.3−5.6 µg/mL) and 19−31% RIF (3.3−4.0 µg/mL), and these results were slightly lower than those for the single-drug systems, reaching 45−81% for FUS (3.8−8.2 µg/mL) and 20−37% for RIF (3.4−4.0 µg/mL). The designed polymer systems show potential as co-delivery systems for combined therapy against drug-resistant strains using two drugs in one formula instead of the separate delivery of two drugs.

The Influence of Polymer Composition on the Hydrolytic and Enzymatic Degradation of Polyesters and Their Block Copolymers with PDMAEMA.

Well-defined, semi-degradable polyester/polymethacrylate block copolymers, based on ε-caprolactone (CL), d,l-lactide (DLLA), glycolide (GA) and N,N'-dimethylaminoethyl methacrylate (DMAEMA), were synthesized by ring-opening polymerization (ROP) and atom transfer radical polymerization. Comprehensive degradation studies of poly(ε-caprolactone)-block-poly(N,N'-dimethylaminoethyl methacrylate) (PCL-b-PDMAEMA) on hydrolytic degradation and enzymatic degradation were performed, and those results were compared with the corresponding aliphatic polyester (PCL). The solution pH did not affect the hydrolytic degradation rate of PCL (a 3% Mn loss after six weeks). The presence of a PDMAEMA component in the copolymer chain increased the hydrolysis rates and depended on the solution pH, as PCL-b-PDMAEMA degraded faster in an acidic environment (36% Mn loss determined) than in a slightly alkaline environment (27% Mn loss). Enzymatic degradation of PCL-b-PDMAEMA, poly(d,l-lactide)-block-poly(N,N'-dimethylaminoethyl methacrylate) (PLA-b-PDMAEMA) and poly(lactide-co-glycolide-co-ε-caprolactone)-block-poly(N,N'-dimethylaminoethyl methacrylate) (PLGC-b-PDMAEMA) and the corresponding aliphatic polyesters (PCL, PLA and PLGC) was performed by Novozyme 435. In enzymatic degradation, PLGC degraded almost completely after eleven days. For polyester-b-PDMAEMA copolymers, enzymatic degradation primarily involved the ester bonds in PDMAEMA side chains, and the rate of polyester degradation decreased with the increase in the chain length of PDMAEMA. Amphiphilic copolymers might be used for biomaterials with long-term or midterm applications such as nanoscale drug delivery systems with tunable degradation kinetics.

Biological In Vitro Evaluation of PIL Graft Conjugates: Cytotoxicity Characteristics.

In vitro cytotoxicity of polymer-carriers, which in the side chains contain the cholinum ionic liquid units with chloride (Cl) or pharmaceutical anions dedicated for antituberculosis therapy, i.e., p-aminosalicylate (PAS) and clavulanate (CLV), was investigated. The carriers and drug conjugates were examined, in the concentration range of 3.125-100 µg/mL, against human bronchial epithelial cells (BEAS-2B) and adenocarcinomic human alveolar basal epithelial cells (A549) as an experimental model cancer cell line possibly coexisting in tuberculosis. The cytotoxicity was evaluated by MTT test and confluency index, as well as by the cytometric analyses, including Annexin-V FITC apoptosis assay. The polymer systems showed supporting activity towards the normal cells and no tumor progress, especially at the highest concentration (100 µg/mL). The analysis of cell death did not show meaningful changes in the case of the BEAS-2B, whereas in the A549 cell line, the cytostatic activity was observed, especially for the drug-free carriers, causing death in up to 80% of cells. This can be regulated by the polymer structure, including the content of cationic units, side-chain length and density, as well as the type and content of pharmaceutical anions. The results of MTT tests, confluency, as well as cytometric analyses, distinguished the polymer systems with Cl/PAS/CLV containing 26% of grafting degree and 43% of ionic units or 46% of grafting degree and 18% of ionic units as the optimal systems.

PDMAEMA/Polyester Miktopolymers: Synthesis via In-Out Approach, Physicochemical Characterization and Enzymatic Degradation.

Synthesis, physicochemical characterization, and the enzymatic degradation of the amphiphilic miktoarm star-shaped polymers is reported herein. First, star-shaped macroinitiators, based on N,N'-dimethylaminoethyl methacrylate (DMAEMA) and glycerol dimethacrylate (GDMA) ((PDMAEMA)n-PGDMA), were synthesized. Due to the presence of hydroxyl groups in the macroinitiator core, polyesters such as poly(ɛ-caprolactone) (P(ɛ-CL)), polylactide (PLA) and poly(lactide-co-glycolide) (PLGA) were synthesized using ring opening polymerization (ROP). Comprehensive degradation studies on enzymatic degradation, using a lipase from Pseudomonas cepacia, were performed. Enzymatic degradation was monitored by weight measurements and nuclear magnetic resonance spectroscopy (1H NMR). The fastest degradation rate was observed for the polymer with the lowest molecular weight. Amphiphilic miktopolymers may find application as biomaterials for long- or mid-term period drug-delivery systems.

Micellar Carriers of Active Substances Based on Amphiphilic PEG/PDMS Heterograft Copolymers: Synthesis and Biological Evaluation of Safe Use on Skin.

Amphiphilic copolymers containing polydimethylsiloxane (PDMS) and polyethylene glycol methyl ether (MPEG) were obtained via an azide-alkyne cycloaddition reaction between alkyne-functionalized copolymer of MPEG methacrylate and azide-functionalized PDMS. "Click" reactions were carried out with an efficiency of 33-47% increasing grafting degrees. The grafted copolymers were able to carry out the micellization and encapsulation of active substances, such as vitamin C (VitC), ferulic acid (FA) and arginine (ARG) with drug loading content (DLC) in the range of 2-68% (VitC), and 51-89% (FA or ARG). In vitro release studies (phosphate buffer saline, PBS; pH = 7.4 or 5.5) demonstrated that the maximum release of active substances was mainly after 1-2 h. The permeability of released active substances through membrane mimicking skin evaluated by transdermal tests in Franz diffusion cells indicated slight diffusion into the solution (2-16%) and their remaining in the membrane. Studies on the selected carrier with FA showed no negative effect on cell viability, proliferation capacity or senescence, as well as cell apoptosis/necrosis differences or cell cycle interruption in comparison with control cells. These results indicated that the presented micellar systems are good candidates for carriers of cosmetic substances according to physicochemical characterization and biological studies.

PEG Graft Polymer Carriers of Antioxidants: In Vitro Evaluation for Transdermal Delivery.

The in vitro biochemical evaluation of the applicability of polymers carrying active substances (micelles and conjugates) was carried out. Previously designed amphiphilic graft copolymers with retinol or 4-n-butylresorcinol functionalized polymethacrylate backbone and poly(ethylene glycol) (PEG) side chains that included Janus-type heterografted copolymers containing both PEG and poly(ε-caprolactone) (PCL) side chains were applied as micellar carriers. The polymer self-assemblies were convenient to encapsulate arbutin (ARB) as the selected active substances. Moreover, the conjugates of PEG graft copolymers with ferulic acid (FA) or lipoic acid (LA) were also investigated. The permeability of released active substances through a membrane mimicking skin was evaluated by conducting transdermal tests in Franz diffusion cells. The biological response to new carriers with active substances was tested across cell lines, including normal human dermal fibroblasts (NHDF), human epidermal keratinocyte (HaCaT), as well as cancer melanoma (Me45) and metastatic human melanoma (451-Lu), for comparison. These polymer systems were safe and non-cytotoxic at the tested concentrations for healthy skin cell lines according to the MTT test. Cytometric evaluation of cell cycles as well as cell death defined by Annexin-V apoptosis assays and senescence tests showed no significant changes under action of the delivery systems, as compared to the control cells. In vitro tests confirmed the biochemical potential of these antioxidant carriers as beneficial components in cosmetic products, especially applied in the form of masks and eye pads.

Micellar Carriers Based on Amphiphilic PEG/PCL Graft Copolymers for Delivery of Active Substances.

Amphiphilic copolymers of alkyne functionalized 2-hydroxyethyl methacrylate (AlHEMA) and poly(ethylene glycol) methyl ether methacrylate (MPEGMA) with graft or V-shaped graft topologies were synthesized. The functionalization of poly(ε-caprolactone) (PCL) with azide group enabled attachment to P(AlHEMA-co-MPEGMA) copolymers via a "click" alkyne-azide reaction. The introduction of PCL as a second side chain type in addition to PEG resulted in heterografted copolymers with modified properties such as biodegradability. "Click" reactions were carried out with efficiencies between 17-70% or 32-50% (for lower molecular weight PCL, 4000 g/mol, or higher molecular weight PCL, 9000 g/mol, respectively) depending on the PEG grafting density. The graft copolymers were self-assembled into micellar superstructures with the ability to encapsulate active substances, such as vitamin C (VitC), arbutin (ARB) or 4-n-butylresorcinol (4nBRE). Drug loading contents (DLC) were obtained in the range of 5-55% (VitC), 39-91% (ARB) and 42-98% (4nBRE). In vitro studies carried out in a phosphate buffer saline (PBS) solution (at pH 7.4 or 5.5) gave the maximum release levels of active substances after 10-240 min depending on the polymer system. Permeation tests in Franz chambers indicated that the bioactive substances after release by micellar systems penetrated through the artificial skin membrane in small amounts, and a majority of the bioactive substances remained inside the membrane, which is satisfactory for most cosmetic applications.

Synthesis and Characterization of Ionic Graft Copolymers: Introduction and In Vitro Release of Antibacterial Drug by Anion Exchange.

Amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethyl- ammonium chloride (TMAMA) were obtained for the delivery of pharmaceutical ionic drugs, such as p-aminosalicylate (PAS) and clavunate (CLV) anions. The side chains were attached by grafting from a multifunctional macroinitiator via atom transfer radical polymerization (ATRP) to get polymers with different grafting degrees and ionic content. The self-assembling ability, confirmed by determining the critical micelle concentration (CMC) through interfacial tension (IFT) with the use of goniometry, was reduced after ion exchange (CMC twice higher than for chloride anions contained copolymers 0.005-0.026 mg/mL). Similarly, the hydrophilicity level (adjusted by the content of ionic fraction) evaluated by the water contact angle (WCA) of the polymer film surfaces was decreased with the increase of trimethylammonium units (68°-44°) and after introduction of pharmaceutical anions. The exchange of Cl- onto PAS- and CLV- in the polymer matrix was yielded at 31%-64% and 79%-100%, respectively. The exchange onto phosphate anions to release the drug was carried out (PAS: 20%-42%, 3.1-8.8 µg/mL; CLV: 25%-73%, 11-31 µg/mL from 1 mg of drug conjugates). Because of the bacteriostatic activity of PAS and the support of the action of the antibiotics by CLV, the designed water-soluble systems could be alternatives for the treatment of bacterial infections, including pneumonia and tuberculosis.

PEG Grafted Polymethacrylates Bearing Antioxidants as a New Class of Polymer Conjugates for Application in Cosmetology.

The amphiphilic copolymers of poly(ethylene glycol) methyl ether methacrylate (MPEGMA) and alkyne functionalized 2-hydroxyethyl methacrylate (AlHEMA) were synthesized by controlled atom transfer radical polymerization (ATRP). The reactions were carried out using the standard ATRP initiator ethyl α-bromoisobutyrate, (EiBBr) and the "bio"initiator bromoester derivative of 4-n-butylresorcinol (4nBREBr2). Two substances with antioxidant activity used in cosmetology, (±)-α-lipoic acid (LA) and ferulic acid (FA), were subjected to esterification reactions to introduce azide groups. The "click" reactions between the alkyne contained copolymers and functionalized acids (LA-N3, FA-N3) were performed to obtain polymer-antioxidant conjugates (P((HEMA-click-FA)-co-MPEGMA) and P((HEMA-click-LA)-co-MPEGMA)). The conjugation was performed with an efficiency of 20-75%. In vitro experiments in a phosphate buffer saline (PBS) solution at neutral conditions demonstrated that the sufficient release was reached after 2.5 h for FA and 1 h for LA. The rapid release kinetics as well as the polymer carriers, which were applied to regulate the delivery of antioxidant substances, are beneficial in cosmetology.