PEG Grafting Research Articles

A thermo-sensitive hydrogel with prominent hemostatic effect prevents tumor recurrence via anti-anoikis-resistance

Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.Graphical

Partially PEG-Grafted Poly(Terphenyl Piperidinium) Anion Exchange Membranes with Balanced Properties for Alkaline Fuel Cells.

Poly(ethylene glycol) (PEG) or oligo (ethylene glycol) (OEG) grafted anion exchange membranes (AEMs) exhibit improved ionic conductivity, high alkaline stability, and subsequent boosted AEM fuel cell performance, but too much PEG/OEG side chains may can result in a reduction in the ion exchange capacity (IEC), which can have adverse effects on ion transport. Here, a series of partially PEG-grafted poly(terphenyl piperidinium) with different side chain length are synthesized using simple postpolymerization modification to produce AEMs with balanced properties. The polar and flexible PEG side chains are responsible for the controlled water uptake and swelling, superior hydroxide conductivity (122 mS cm-1 at 80 °C with an IEC of 1.99mmol g-1), and enhanced alkaline stability compared to the reference sample without PEG grafts (PTP). More importantly, the performance of AEM fuel cell (AEMFC) with the membrane containing partial PEG side chains surpasses that with PTP membrane, demonstrating a highest peak power density of 1110mW cm-2 at 80 °C under optimized conditions. This work provides a novel approach to the fabrication of high-performance AEM materials with balanced properties for alkaline fuel cell application.

Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis

Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe3+) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe3+ and EGCG. The released Fe3+ produces large amounts of toxic •OH by the Fenton reactions while having minimal impact on normal cells. The generated •OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of •OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.

Inhibition of non-specific protein adsorption on PMMA surface: The role of surface modification

Mitigating non-specific adsorption (NSA) occurring on the surface of microfluidic devices plays a critical role in the detection of early protein biomarkers for clinical diagnosis. Surface-modified methods commonly used in the formation of microfluidic channels include BSA coating, PEG grafting, and Plasma cleaning. The surface composition and microstructure of PMMA surfaces were characterized by Fourier transfer infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), water contact angles (CA), and atomic force microscopy (AFM) measurements. The NSA on surfaces of bovine serum albumin (BSA) labeled with fluorescein isothiocyanate (FITC) were investigated by microfluidics and fluorescence microscopy. The results showed that the hydrophobicity of the PMMA surface was enhanced after modification with PEG. We further evaluated their anti-protein adsorption properties under a mild alkaline (PH 7.4) condition, including concentration, reaction time, and sample volume. The BSA coating had the best anti-protein adsorption effect, reaching over 87.6%. The anti-protein adsorption effect of the plasma cleaning method is slightly inferior to that of BSA coating, at 86.1%, but the modification process is simpler and faster. Due to the insufficient stability of PEG, its resistance to protein adsorption decreases as the concentration increases.

PEGylated insulin loaded complexation hydrogels for protected oral delivery

While a number of enteric coatings and pH-sensitive oral delivery vehicles have been developed, they lack the ability to sufficiently protect proteins from proteolytic degradation once released from the carrier. In this work, we show that H-bonded, pH-sensitive poly(methacrylic acid-grafted ethylene glycol) glycol (henceforth designated as P(MAA-g-EG) gels) exhibit great promise as protein carriers, as they utilize poly(ethylene glycol) (PEG) chains to promote mucoadhesion in the small intestine, increasing the chances that the drug is released within the villus of the absorptive intestinal wall. Importantly, PEG was also conjugated to the B29-lysine (LysB29) position of insulin in order to protect the drug from proteolytic degradation once released in the small intestine and adhere the drug to the intestinal epithelium through improved mucoadhesion. PEG-conjugated (PEGylated) molecules were found to actively participate in the carrier loading and release mechanism, with the drug conjugate hydrogen bonding to the MAA while in the collapsed state and subsequently repulse the drug above the polymer's isoelectric point. This effect was enhanced through the evaluation of PEG graft density within the carrier. Cellular transport and changes in transepithelial resistance caused by the PEGylated insulin (PI) in the presence of P(MAA-g-EG) microparticles were analyzed using a 1:1 co-culture of human colon adenocarcinoma (Caco-2) and: the mucus-secreting human colon carcinoma cell(HT-29-MTX). Finally, the in vivo absorption of insulin was measured in Sprague-Dawley rats to ensure that the PEGylated insulin conjugates are biologically active, as well as to compare the bioavailability to control insulin. Collectively, these results lead toward the development of a novel system for improved insulin delivery, with improved stability of insulin through PEGylation.

One-Step Bulk-Suspension Polymerization of Polyethylene Glycol-Based Copolymer Microspheres for Phase Change Textiles.

The paper presents a feasible strategy through one-step bulk-suspension polymerization, grafting PEG onto an in situ synthesized copolymer. In more detail, PEG was grafted onto a homemade polystyrene/maleic anhydride copolymer (SMA) via bulk-suspension polymerization with poly(vinyl alcohol) as a suspending agent. According to the optimal reaction conditions, the grafting rate of PEG was 56.2% through chemical titration experiments. At the same time, the quantitative relationship between the grafting rate and enthalpy was demonstrated for the first time in a PEG-based solid-solid phase change material (S-SPCM). Morphology observation revealed that the obtained S-SPCM is made up of white microspheres of approximately 100-150 μm. The powdery product polystyrene/maleic anhydride grafted polyethylene glycol (SMA-g-PEG) obtained through bulk-suspension polymerization endowed that the whole product could be used directly as a phase change material without postprocessing. The melting enthalpy and crystallization enthalpy of SMA-g-PEG were 79.3 J/g and 76.9 J/g, respectively. Based on the effective fixed load of PEG, the macrostructure of SMA-g-PEG was almost unchanged at 70 °C compared with the macrostructures at 20 °C, and the latent heat of SMA-g-PEG was decreased slightly after 1000 thermal cycles. Overall, the obtained SMA-g-PEG can be used as a filler in insulation materials and composited with fibers to obtain phase change thermoregulated smart textiles.

Survivorship of Allologous Structural Bone Graft at a Minimum of 2 Years When Used to Address Significant Glenoid Bone Loss in Revision Shoulder Arthroplasty: A Computed Tomographic and Clinical Review.

This study assesses outcomes in revision shoulder replacements where the glenoid bone loss was managed using a structural allograft (donated femoral head) in combination with a trabecular titanium (TT) implant. We contacted patients who had undergone revision shoulder arthroplasty using the Lima Axioma TT metal-backed glenoid with an allologous bone graft as a composite who were over 2 years since surgery. Patients underwent computerd tomography evaluation, clinical review, and scoring preoperatively, at 6 months and the latest follow-up. Fifteen patients were included with a mean age of 59 (33-76). The average follow-up period was 40.5 months (24-51). 80% showed satisfactory bone graft incorporation and peg integration at the latest follow-up. Three had signs of significant bone graft resorption, although in 2 patients the pegs were still soundly fixed in the host bone. Clinically all patients showed a statistically significant improvement in pain relief, movement, and function. No unusual complications were reported. Results show femoral head structural allograft in combination with TT metal-backed glenoid baseplate is a viable option for revision total shoulder replacement in the context of massive glenoid bone loss. We do, however, acknowledge that this resorption rate is higher than in other reported series where autograft is used.

Anti-fouling membranes for organic solvent nanofiltration (OSN) and organic solvent ultrafiltration (OSU): graft modified polybenzimidazole (PBI)

Fouling is one of the major obstacles to successful membrane-based separations. In aqueous systems, fouling is well characterised and fouling reduction techniques are established. However, in organic solvents, membrane fouling is not well understood. In this work we manufactured anti-fouling organic solvent stable polybenzimidazole (PBI) membranes by graft modifying the surface with linear poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG). Graft modification provided an effective method of reducing fouling. However, the anti-fouling properties were dependent on the interactions between the modifying polymer and the solvent. In water, the hydrophilic PEG graft modifiers had favourable modifier-water interactions and provided an anti-fouling steric layer on the surface of the membrane. However, hydrophobic PPG graft modifiers had unfavourable modifier-water interactions and provided no anti-fouling properties. Conversely, in polar organic solvents, graft modification with PPG showed superior modifier-solvent interactions, and superior anti-fouling properties, relative to graft modification with the same molecular weight PEG. In non-polar solvents, both the PEG and PPG modifiers had unfavourable modifier-solvent interactions and provided minimal anti-fouling properties. The anti-fouling properties after graft modification were closely correlated to the hydrodynamic diameter of the grafting polymer in solution, and the selection of an optimal grafting polymer for manufacturing anti-fouling OSN and OSU membranes is significantly solvent dependant.

Human blood biocompatibility and immunogenicity of scFvD2B PEGylated gold nanoparticles

Single chain variable D2B antibody fragments (scFvD2Bs) exhibit high affinity binding to prostate specific membrane antigens overexpressed in metastatic prostate cancer (PC). Conjugation of scFvD2B to gold nanoparticles (AuNPs) would enhance its stability and plasma half-life circulation to shuttle theranostic agents in PC. In this study, we synthesized PEGylated scFvD2B-AuNPs (AuNPs-scFvD2B-PEG) and tested their integrity, biocompatibility, and immunogenicity in freshly withdrawn human blood. Prior to blood incubation, Zeta potential measurements, UV–Vis spectroscopy, and dynamic light scattering (DLS) were used to assess the physicochemical properties of our nano-complexes in the presence or absence of PEGylation. A surface plasmon resonance band shift of 2 and 4 nm confirmed the successful coating for AuNPs-scFvD2B and AuNPs-scFvD2B-PEG, respectively. Likewise, DLS revealed a size increase of ∼3 nm for AuNPs-scFvD2B and ∼19 nm for AuNPs-scFvD2B-PEG. Zeta potential increased from −34 to −19 mV for AuNPs-scFvD2B and reached −3 mV upon PEGylation. Similar assessment measures were applied post-incubation in human blood with additional immunogenicity tests, such as hemolysis assay, neutrophil function test, and pyridine formazan extraction. Interestingly, grafting PEG chains on AuNPs-scFvD2B precluded the binding of blood plasma proteins and reduced neutrophil activation level compared with naked AuNPs-citrate counterparts. Most likely, a hydrated negative PEG cloud shielded the NPs rendering blood compatiblility with less than 10% hemolysis. In conclusion, the biocompatible AuNPs-scFvD2B-PEG presents promising characteristics for PC targeted therapy, with minimal protein adsorption affinity, low immunorecognition, and reduced hemolytic activity.

Mitochondria-targeting polydopamine-coated nanodrugs for effective photothermal- and chemo-synergistic therapies against lung cancer.

Targeting mitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance. Here, a mitochondria-targeting nanoparticle (TOS-PDA-PEG-TPP) was designed to precisely deliver polydopamine (PDA) as the photothermal agent and alpha-tocopherol succinate (α-TOS) as the chemotherapeutic drug to the mitochondria of the tumor cells, which inhibits the tumor growth through chemo- and photothermal- synergistic therapies. TOS-PDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled by α-TOS, followed by grafting PEG and triphenylphosphonium (TPP) on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells. In vitro studies showed that TOS-PDA-PEG-TPP could be efficiently internalized by tumor cells and accumulated at mitochondria, resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation. In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects. Conclusively, the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.

Polyethylene glycol grafted chitin nanocrystals enhanced, stretchable, freezing-tolerant ionic conductive organohydrogel for strain sensors

Ionic conductive hydrogels with advantageous mechanical properties and high stretchability attract much attentions in wearable electronic devices. Here, a freezing-tolerant hydrogel with high stretchability (435%), strength (2.0 MPa), and ionic conductivity had been prepared by freezing/thawing of polyvinyl alcohol (PVA) and polyethylene glycol functionalized chitin nanocrystals (PEG-g-ChNCs) in dimethyl sulfoxide-water solvent. The successful grafting of PEG on ChNCs was confirmed by various characterization methods. The organohydrogel reinforced by PEG-g-ChNCs displayed excellent freezing-tolerance without rupture during extension, which remains conductivity (0.01 S/m) even at −20 °C. PVA/PEG-g-ChNCs organohydrogel was employed as strain sensor. Interestingly, the sensors based on this organohydrogel presented high stretching sensitivity with a gauge factor of 2.3, and it could be repeatedly and stably monitor tiny strain under extension and pressure. Therefore, the ionic conductive organohydrogel sensor based PEG-g-ChNCs enhanced PVA have promising applications in wearable devices, such as sports monitoring or healthcare monitoring.

Instantaneous Degelling Thermoresponsive Hydrogel.

Responsive polymeric hydrogels have found wide application in the clinic as injectable, biocompatible, and biodegradable materials capable of controlled release of therapeutics. In this article, we introduce a thermoresponsive polymer hydrogel bearing covalent disulfide bonds. The cold aqueous polymer solution forms a hydrogel upon heating to physiological temperatures and undergoes slow degradation by hydrolytic cleavage of ester bonds. The disulfide functionality allows for immediate reductive cleavage of the redox-sensitive bond embedded within the polymer structure, affording the option of instantaneous hydrogel collapse. Poly(ethylene glycol)-b-poly(lactic acid)-S-S-poly(lactic acid)-b-poly(ethylene glycol) (PEG-PLA-SS-PLA-PEG) copolymer was synthesized by grafting PEG to PLA-SS-PLA via urethane linkages. The aqueous solution of the resultant copolymer was a free-flowing solution at ambient temperatures and formed a hydrogel above 32 °C. The immediate collapsibility of the hydrogel was displayed via reaction with NaBH4 as a relatively strong reducing agent, yet stability was displayed even in glutathione solution, in which the polymer degraded slowly by hydrolytic degradation. The polymeric hydrogel is capable of either long-term or immediate degradation and thus represents an attractive candidate as a biocompatible material for the controlled release of drugs.

Grafting PEG on cellulose nanocrystals via polydopamine chemistry and the effects of PEG graft length on the mechanical performance of composite film

In this study, cellulose nanocrystals (CNCs) with PEG grafts of various lengths (1 k, 2 k, 5 k, and 10 kDa) were prepared via a polydopamine (PDA) mediated method in the aqueous solution. The prepared CNC-PEGs were further used to reinforce the polyvinyl alcohol (PVA) at the loading of 0, 1, 3, 5, and 7 wt% in order to demonstrate the effects of the PEG length on the properties of the PVA/CNC nanocomposites. PEG surface modification resulted in simultaneous improvements in stiffness and toughness. The graft lengths have noticeable impacts on the properties of composites. The shorter graft yields better enhancement in strength and stiffness, attributable to the high efficiency in the stress transfer and high interface adhesion. The longer PEG graft length yields high graft-matrix entanglement, forming a thicker rubbery coating layer that enhances the toughness of PVA/CNC composites.

ENHANCING HYDROPHILICITY OF POLYSULFONE MEMBRANE SURFACE BY UV IRRADIATION OF DIFFERENT WAVELENGTHS AND BY PEG GRAFTING

Polysulfone polymer (PSF) membrane has disadvantages due to its hydrophobicity, which may cause fouling and reduce separation performance. Therefore, this study aimed to enhance the hydrophilicity of PSF membranes by using irradiation at different ultraviolet (UV) wavelengths, followed by Poly(ethylene glycol) (PEG) grafting on the PSF surfaces. The hydrophilicity of the treated membrane surfaces was examined by measuring water contact angle (WCA), surface energy (SE), surface morphology, functional groups, salt rejection, and water flux in a filtration instrument. The results show that with long UV treatment for up to 72 h, the 312 nm wavelength gave lesser WCA than treatment at 254 nm. The treated PSF membrane irradiated at 312 nm for 72 h, followed by PEG grafting, was effectively improved and retained increased hydrophilicity for up to thirty days.

Multi-Analytical Framework to Assess the In Vitro Swallowability of Solid Oral Dosage Forms Targeting Patient Acceptability and Adherence.

A lack of effective intervention in addressing patient non-adherence and the acceptability of solid oral dosage forms combined with the clinical consequences of swallowing problems in an ageing world population highlight the need for developing methods to study the swallowability of tablets. Due to the absence of suitable techniques, this study developed various in vitro analytical tools to assess physical properties governing the swallowing process of tablets by mimicking static and dynamic stages of time-independent oral transitioning events. Non-anatomical models with oral mucosa-mimicking surfaces were developed to assess the swallowability of tablets; an SLA 3D printed in vitro oral apparatus derived the coefficient of sliding friction and a friction sledge for a modified tensometer measured the shear adhesion profile. Film coat hydration and in vitro wettability was evaluated using a high-speed recording camera that provided quantitative measurements of micro-thickness changes, simulating static in vivo tablet–mucosa oral processing stages with artificial saliva. In order to ascertain the discriminatory power and validate the multianalytical framework, a range of commonly available tablet coating solutions and new compositions developed in our lab were comparatively evaluated according to a quantitative swallowability index that describes the mathematical relationship between the critical physical forces governing swallowability. This study showed that the absence of a film coat significantly impeded the ease of tablet gliding properties and formed chalky residues caused by immediate tablet surface erosion. Novel gelatin- and λ-carrageenan-based film coats exhibited an enhanced lubricity, lesser resistance to tangential motion, and reduced stickiness than polyvinyl alcohol (PVA)–PEG graft copolymer, hydroxypropyl methylcellulose (HPMC), and PVA-coated tablets; however, Opadry® EZ possessed the lowest friction–adhesion profile at 1.53 a.u., with the lowest work of adhesion profile at 1.28 J/mm2. For the first time, the in vitro analytical framework in this study provides a fast, cost-effective, and repeatable swallowability ranking method to screen the in vitro swallowability of solid oral medicines in an effort to aid formulators and the pharmaceutical industry to develop easy-to-swallow formulations.

Impact of dynamic sub-populations within grafted chains on the protein binding and colloidal stability of PEGylated nanoparticles.

Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction, to extend blood circulation times and to modulate protein recognition and cellular uptake. However, the role of PEG graft dynamics and conformation in determining surface recognition processes is poorly understood primarily due to the absence of a microscopic picture of the surface presentation of the polymer. Here a detailed NMR analysis reveals three types of dynamic ethylene glycol units on PEG-grafted SiO2 nanoparticles (NPs) of the type commonly evaluated as long-circulating theranostic nano-probes; a narrow fraction with fast dynamics associated with the chain ends; a broadened fraction spectrally overlapped with the former arising from those parts of the chain experiencing some dynamic restriction; and a fraction too broad to be observed in the spectrum arising from units closer to the surface/graft which undergo slow motion on the NMR timescale. We demonstrate that ethylene glycol units transition between fractions as a function of temperature, core size, PEG chain length and surface coverage and demonstrate how this distribution affects colloidal stability and protein uptake. The implications of the findings for biological application of grafted nanoparticles are discussed in the context of accepted models for surface ligand conformation.

The stepwise organization of nanoparticles into a Pickering emulsion.

Core/shell PVSt-b-PS@Fe3O4 composite nanoparticles (NPs) are achieved by grafting living cationic block copolymer chains onto the surface of amine-capped Fe3O4 NPs via fast termination. The number of chains grafted can be tuned via the molecular weight of PVSt-b-PS. Upon grafting PEG onto the PVSt block via a click reaction, the resulting (PVSt-g-PEG)-b-PS@Fe3O4 composite NPs become highly dispersible in water. A composite nanoparticle with ten chains is selected as a homogeneous NP to demonstrate the dynamic stepwise organization of the NP as oil is fed into the aqueous dispersion. The individual NPs with captured oil are further aggregated, but remain stable with increasing oil content. Eventually, a Pickering emulsion forms in which the aggregates are anchored at the emulsion interface. This dynamic behavior study helps to provide an understanding of the mechanism by which NPs stabilize Pickering emulsions.

Thermally-induced hyperbranching of bromine-containing polyesters by insertion of in situ generated chain-end carbenes.

Hyperbranched, biodegradable PCL-based polymers are obtained through a random but invasive migration of an in situ generated carbene end group which is unmasked via the thermolysis of its precursor diazirine moiety. These hyperbranched cores are used as macroinitiators for 'grafting-from' polymerisation using controlled radical polymerisation to achieve amphiphilic copolymers which can subsequently be self-assembled into spherical core-shell micelles.

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.