Hydrolytic Degradation Rate Research Articles

Accelerated hydrolytic degradation of poly(l-lactide) by blending with poly(ether-block-amide)

A continuing challenge in the most common biodegradable polyester of poly(l-lactide) (PLLA) is to improve the degradation rate in the environment, though it has been widely used in packaging and medical applications. In this study, PLLA/poly(ether-block-amide) (PEBA) blends are prepared by melt blending to investigate the effect of PEBA component on the phase morphology, thermal behavior, mechanical properties, and hydrolytic degradation of the blends. The incorporation of PEBA component is beneficial to the improved toughness and increased water absorption of the blends, and accelerated hydrolytic degradation of PLLA. The blend exhibits the optimal mechanical and hydrolytic degradation properties when the blend mass ratio of PLLA/PEBA is 80/20. The toughness of the blend is increased by 390 % compared to that of pure PLLA. After being hydrolyzed at 58 °C for 240 h, the water absorption, the mass loss and the decrease of molecular weight of the blend is increased by 138 %, 160 % and 40 %, respectively, indicating faster hydrolytic degradation rate of the blend than that of pure PLLA. Furthermore, the accelerated hydrolytic degradation mechanism of PLLA in the blend is revealed. The amorphous region of PLLA is hydrolyzed initially at the phase interface of the blend, and subsequently the crystalline structure of PLLA is degraded. The hydrolysis process causes a change in the relative content of crystalline regions in the system, resulting in an increase in crystallinity of PLLA first and then decrease. These findings provide a new strategy for the design of novel degradable PLLA materials for practical applications.

Hydrolysis kinetics of self-degradable diverters for well stimulation

Self-degradable diverters have gained increased popularity in well stimulation as an environmentally friendly and robust fluid diversion technology. As of now, limited data and conflicting information exist in the literature regarding the hydrolytic degradation rates of diverters under field-representative conditions, and knowing these rates is crucial for optimizing well stimulation designs. In this work, we systematically measured the degradation rates of commercial self-degradable diverters in aqueous solutions spanning a wide solution pH range of 0.3–13.6 and a wide temperature range of 60–110 °C. We first demonstrated that existing bottle degradation test protocols might return misleading results due to the alteration of solution pH by degradation products, and we developed a more reliable experimental protocol using buffer solutions instead. Using this procedure, we found that as the solution pH increased, the hydrolysis rate of diverters first decreased and then increased, with a minimal degradation rate at around pH = 4. Elevated temperatures yielded faster hydrolysis. The collected kinetic data fit reasonably well to a published kinetic model that was originally developed for pure polylactic acid in deionized water, with an R2 value over 0.98 for all pH and temperature conditions. This comparison suggests that the model can be more widely applied to describe the degradation kinetics of commercial diverters over broad temperature and pH ranges. The test protocol, experimental data, and kinetic analysis in this work provide important guidance on improving the efficiency of fluid diversion and well stimulation operations.

Osteogenic differentiation of human adipose-derived stem cells on polycaprolactone 3D-printed scaffolds containing bioactive bioceramic

Three-dimensional (3D) printing is a promising approach to fabricating bone tissue engineering scaffolds with desired geometry and properties. In this study, we hypothesized that a post-fabrication modification process with baghdadite as a bioactive glass can improve the osteoconductivity of PCL-based 3D-printed scaffolds. The main advantage of this study is the introduction of a cost-effective post-fabrication process for the treatment of 3D-printed porous scaffold for bone tissue engineering applications. The 3D-printed scaffolds were fabricated with circular four-layer and lay-down 0/90°patterns, before exposing them to three different concentrations of baghdadite (1 %, 5 %, and 10 %). The results showed that the addition of baghdadite to the PCL scaffolds did not alter the mechanical behavior of the scaffold. However, the hydrolytic degradation rate was higher for PCL/baghdadite than for plasma-treated scaffold. The biocompatibility of human adipose tissue-derived mesenchymal stem cells (hASCs) cultured on the scaffolds was evaluated by MTT and live/dead staining assays. The osteogenic differentiation ability of scaffolds was measured by evaluating alkaline phosphatase (ALP) activity, calcium deposition, and four bone-related gene expressions (osteocalcin, osteonectin, ALP, and RUNX). The results revealed that the surface treatment of printed scaffolds significantly improved the osteogenic differentiation of hASCs culture on scaffolds and therefore this method can be an effective approach for the treatment of bone tissue engineering scaffolds.

Industrial-scale needle-less electrospinning of tetracycline-immobilized nanofibrous scaffolds using a polycaprolactone/polyethylene oxide/chitosan blend for wound healing

Nanofibrous scaffolds offer significant promise for wound healing due to their ability to absorb exudates, prevent microbial contamination, and enhance oxygen diffusion. However, challenges remain in fully realizing their clinical potential, as previous research has primarily focused on scaffolds made of two polymers or those encapsulating therapeutic agents within nanofibers. Additionally, scaling up fabrication while maintaining functionality presents a significant challenge. This study introduces a novel type of nanofibrous scaffold, combining poly (ethylene oxide) (PEO), poly (caprolactone) (PCL), and chitosan (CS) in various mass ratios, electrospun using Nanospider™ technology. The scaffolds featured fiber diameters ranging from 134 ± 37 to 148 ± 38 nm and exhibit high gram-per-square-meter values between 6.8 and 8.6 g/m2. An optimal balance of hydrophilicity was achieved, and the scaffolds demonstrated superior breathability with moisture vapor transmission rates ranging from 1904.3 ± 28.6 to 2005.7 ± 42.9 g/m2/day, outperforming commercial wound dressings. Additionally, a wide range of hydrolytic degradation rates (3.8 ± 1% to 73.2 ± 0.8%), elongation at fracture (21% to 0.8%), and Young’s modulus (106.7 ± 8.5 MPa to 170.7 ± 11.9 MPa) were observed. Surface-immobilized tetracycline (TET) significantly enhanced antibacterial efficacy, with inhibition zones exceeding 20 mm against Escherichia coli. Our findings confirm that scaffold properties can be effectively tailored by adjusting the PEO/PCL ratio, advancing customization for wound care. Post-fabrication soaking in TET solutions further boosts antibacterial performance and allows for tailored post-production adjustments. Compared to existing studies, this approach simplifies customization and improves the practicality of wound care solutions.

Toward chronopharmaceutical drug delivery patches and biomaterial coatings for the facilitation of wound healing

Implantation of a biomaterial entails a form of injury where the integration of the implant into the host tissue greatly depends on the proper healing of the wound. Wound healing, itself, consists of a number of physiological processes, each occurring within a characteristic time window. A composite, multilayered polymeric drug delivery carrier for adhesion to the wound site and its supply with molecules released at precise time windows at which the stages in the healing process that they target occur is conceptualized here. We also present a simplified version of one such multilayered composite fabricated by a combination of solvent casting and dip coating, comprising the base poly(ε-caprolactone) layer reinforced with hydroxyapatite nanoparticles, poly(glutamic acid) mesolayer and poly-l-lysine surface layer, each loaded with specific small molecules and released at moderately distinct timescales, partially matching the chronology of wound healing. To that end, the base layer proved suitable for the delivery of an anti-inflammatory molecule or an angiogenic agent, the mesolayer appeared appropriate for the delivery of an epithelialization promoter or a granulation factor, and the adhesive surface layer interfacing directly with the site of injury showed promise as a carrier of a vasodilator. The drug release mechanisms were diffusion-driven, suggesting that the drug/carrier interaction is a key determinant of the release kinetics, as important as the nature of the polymer and its hydrolytic degradation rate in the aqueous medium. Morphological and phase composition analyses were performed, along with the cell compatibility ones, demonstrating solid adhesion and proliferation of both transformed and primary fibroblasts on both surfaces of the composite films. The design of the multilayered composite drug delivery carriers presented here is prospective, but requires further upgrades to achieve the ideal of a perfect timing of the sequential drug release kinetics and a perfect resonance with the physiological processes defining the chronology of wound healing.

Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency.

The inclusion of fluorine motifs in drugs and drug delivery systems is an established tool for modulating their biological potency. Fluorination can improve drug specificity or boost the vehicle's ability to cross cellular membranes. However, the approach has yet to be applied to vaccine adjuvants. Herein, the synthesis of fluorinated bioisostere of a clinical stage immunoadjuvant-poly[di(carboxylatophenoxy)phosphazene], PCPP-is reported. The structure of water-soluble fluoropolymer-PCPP-F, which contains two fluorine atoms per repeat unit-was confirmed using 1H, 31P and 19F NMR, and its molecular mass and molecular dimensions were determined using size-exclusion chromatography and dynamic light scattering. Insertion of fluorine atoms in the polymer side group resulted in an improved solubility in acidic solutions and faster hydrolytic degradation rate, while the ability to self-assemble with an antigenic protein, lysozyme-an important feature of polyphosphazene vaccine adjuvants-was preserved. In vivo assessment of PCPP-F demonstrated its greater ability to induce antibody responses to Hepatitis C virus antigen when compared to its non-fluorinated counterpart. Taken together, the superior immunoadjuvant activity of PCPP-F, along with its improved formulation characteristics, demonstrate advantages of the fluorination approach for the development of this family of macromolecular vaccine adjuvants.

Smart collagen/xanthan gum-based hydrogels with antibacterial effect, drug release capacity and excellent performance in vitro bioactivity for wound healing application

The design of hydrogels based on natural polymers that have modulation of antibacterial capacity, ideal performance in release capacity of encapsulated drugs, and desired bioactivity for applications in wound healing represents a modern trend in biomaterials. In this work, novel hydrogels of semi-interpenetrating polymeric networks based on collagen and xanthan gum (XG) were investigated. The linear chains of XG can semi-interpenetrate inside to matrix of crosslinked collagen with polyurethane under physiological conditions, generating amorphous surfaces with fibrillar-granular reliefs that have accelerated gelation time (about 15 min), super water absorption (up to 3100%) and high inhibition capacity of pathogenic bacteria such as Escherichia coli (up to 100% compared to amoxicillin at 20 ppm). The increment of XG in the hydrogel (up to 20 wt.%) allows for improvement in the storage module, resistance to thermal degradation, slow the rate of hydrolytic and proteolytic degradation, allowing to encapsulate and controlled release of molecules such as ketorolac and methylene blue; besides, it shows to keep the metabolic activity of fibroblasts and monocytes at 48 h of evaluation, without observing cytotoxic effects. The bioactivity of these hydrogels is improved since they have excellent hemocompatibility and enhanced cell proliferation. Specifically, the hydrogel with 20 wt.% of XG shows to decrease the production of tumor necrosis factor-α and CCL-2 cytokines, increasing the production of transforming growth factor-β in human monocytes, which could be used to modulate inflammation and regenerative capacity in wound healing strategies.

Enhanced Tensile Properties, Biostability, and Biocompatibility of Siloxane-Cross-Linked Polyurethane Containing Ordered Hard Segments for Durable Implant Application.

This work developed a series of siloxane-modified polyurethane (PU-Si) containing ordered hard segments by a facile method. The polyaddition between poly(ε-caprolactone) and excess diurethane diisocyanate was carried out to synthesize a polyurethane prepolymer with terminal isocyanate groups, which was then end-capped by 3-aminopropyl triethoxysilane to produce alkoxysilane-terminated polyurethane; the target products of PU-Si were obtained with hydrolysis and the condensation of alkoxysilane groups. The chemical structures were confirmed by FT-IR and XPS, and the effect of the siloxane content or cross-linked degree on the physicochemical properties of the PU-Si films was investigated in detail. The formation of the network structure linked by Si-O-Si bonds and interchain denser hydrogen bonds endowed PU-Si films with fine phase compatibility, low crystallinity, high thermal stability, and excellent tensile properties. Due to the high cross-linked degree and low interfacial energy, the films displayed a high surface water contact angle and low equilibrium water absorption, which resulted in slow hydrolytic degradation rates. Furthermore, the evaluation of protein adsorption and platelet adhesion on the PU-Si film surface presented high resistance to biofouling, indicating superior surface biocompatibility. Consequently, the siloxane-cross-linked polyurethane, which possessed excellent tensile properties, high biostability, and superior biocompatibility, showed great potential to be explored as biomaterials for durable implants.

Electrically conductive scaffolds mimicking the hierarchical structure of cardiac myofibers

Electrically conductive scaffolds, mimicking the unique directional alignment of muscle fibers in the myocardium, are fabricated using the 3D printing micro-stereolithography technique. Polyethylene glycol diacrylate (photo-sensitive polymer), Irgacure 819 (photo-initiator), curcumin (dye) and polyaniline (conductive polymer) are blended to make the conductive ink that is crosslinked using free radical photo-polymerization reaction. Curcumin acts as a liquid filter and prevents light from penetrating deep into the photo-sensitive solution and plays a central role in the 3D printing process. The obtained scaffolds demonstrate well defined morphology with an average pore size of 300 ± 15 μm and semi-conducting properties with a conductivity of ~ 10–6 S/m. Cyclic voltammetry analyses detect the electroactivity and highlight how the electron transfer also involve an ionic diffusion between the polymer and the electrolyte solution. Scaffolds reach their maximum swelling extent 30 min after immersing in the PBS at 37 °C and after 4 weeks they demonstrate a slow hydrolytic degradation rate typical of polyethylene glycol network. Conductive scaffolds display tunable conductivity and provide an optimal environment to the cultured mouse cardiac progenitor cells.

Effect of the content of starch on the biocompatibility, bacterial inhibition, and drug release performance of semi-IPN collagen-polyurethane hydrogels

This work studied the effect of content of starch on the structure and properties of hydrogels generated by semi-interpenetrating the polysaccharide in the collagen-polyurethane matrix and generating biomaterials in the hydrogel state potentially useful in biomedicine. Starch increased the reticulation of the polymeric matrix by hydrogen bonding with the collagen fibers. The maximum swelling degree was observed for the formulation containing 40 wt.% of starch. The microstructure of these materials is semi-crystalline and the increase of the content of starch avoids the segregation of starch granules in the matrix, generating homogeneous surfaces that tend to release less glucose-rich degradation by-products and encapsulated ketorolac. Materials with low content of starch (10–20 wt.%) improve both the mechanical and thermal stability of the hydrogels and the ketorolac release performance. The matrices activated the metabolism of monocytes and fibroblasts, favoring their proliferation. The presence of starch in semi-IPN hydrogels confers high inhibition capacity of E. coli and a slow rate of hydrolytic and proteolytic degradation. The results of cell signaling for important cytokines in the wound healing process indicated that the CS20% matrix shows favorable modulation of TNF-α, MCP-1, and TGF-β secretion, so it could be successfully applied in the treatment of chronic wounds.

Chemically Crosslinked Amphiphilic Degradable Shape Memory Polymer Nanocomposites with Readily Tuned Physical, Mechanical, and Biological Properties.

Facile surgical delivery and stable fixation of synthetic scaffolds play roles just as critically as degradability and bioactivity in ensuring successful scaffold-guided tissue regeneration. Properly engineered shape memory polymers (SMPs) may meet these challenges. Polyhedral oligomeric silsesquioxanes (POSSs) can be covalently integrated with urethane-crosslinked polylactide (PLA) to give high-strength, degradable SMPs around physiological temperatures. To explore their potential for guided bone regeneration, here we tune their hydrophilicity, degradability, cytocompatibility, and osteoconductivity/osteoinductivity by crosslinking star-branched POSS-PLA with hydrophilic polyethylene glycol diisocyanates of different lengths and up to 60 wt % hydroxyapatite (HA). The composites exhibit high compliance, toughness, up to gigapascal storage moduli, and excellent shape recovery (>95%) at safe triggering temperatures. Water swelling ratios and hydrolytic degradation rates positively correlated with the hydrophilic crosslinker lengths, while the negative impact of degradation on the proliferation and osteogenesis of bone marrow stromal cells was mitigated with HA incorporation. Macroporous composites tailored for a rat femoral segmental defect were fabricated, and their ability to stably retain and sustainedly release recombinant osteogenic bone morphogenetic protein-2 and support cell attachment and osteogenesis was demonstrated. These properties combined make these amphiphilic osteoconductive degradable SMPs promising candidates as next-generation synthetic bone grafts.

Effect of gamma-irradiation on hydrolysis of commercial poly(L-lactide) at elevated temperature

The present study aimed to examine the effect of gamma-irradiation on subsequent hydrolytic degradation of poly(L-lactide) (PLLA) and polymer crystallization behavior during this process. Absorbed doses were 29 and 75 kGy, unirradiated sample was also studied. Hydrolysis was performed at 60 °C for up to 50 days. Radiation treatment of PLLA accelerates hydrolysis process. It affects polymer mass loss, molecular weight distribution, change of hydrolysis media pH, and values of the hydrolytic degradation rate constant. Preliminary irradiation makes it possible to eliminate the induction period of PLLA mass loss during hydrolysis. However, a decrease of polymer molecular weight during irradiation leads to an increase of PLLA crystallization rate upon hydrolysis. It was found that α crystals can be formed during hydrolytic degradation. Parameters of PLLA unit cell were calculated. When polymer degree of crystallinity becomes high enough its hydrolytic degradation slows down. Thus, faster crystallization of irradiated PLLA reduces the acceleration effect of radiation treatment on polymer hydrolysis.

Maleic Anhydride-Grafted PLA Preparation and Characteristics of Compatibilized PLA/PBSeT Blend Films.

Poly(butylene sebacate-co-terephthalate) (PBSeT) is a biodegradable flexible polymer suitable for melt blending with other biodegradable polymers. Melt blending with a compatibilizer is a common strategy for increasing miscibility between polymers. In this study, PBSeT polyester was synthesized, and poly(lactic acid) (PLA) was blended with 25 wt% PBSeT by melt processing with 3–6 phr PLA-grafted maleic anhydride (PLA-g-MAH) compatibilizers. PLA-g-MAH enhanced the interfacial adhesion of the PLA/PBSeT blend, and their mechanical and morphological properties confirmed that the miscibility also increased. Adding more than 6 phr of PLA-g-MAH significantly improved the mechanical properties and accelerated the cold crystallization of the PLA/PBSeT blends. Furthermore, the thermal stabilities of the blends with PLA-g-MAH were slightly enhanced. PLA/PBSeT blends with and without PLA-g-MAH were not significantly different after 120 h, whereas all blends showed a more facilitated hydrolytic degradation rate than neat PLA. These findings indicate that PLA-g-MAH effectively improves PLA/PBSeT compatibility and can be applied in the packaging industry.

Gradient versus End-Capped Degradable Polymer Sequence Variations Result in Stiff to Elastic Photochemically 3D-Printed Substrates.

Additive manufacturing affords the construction of complex scaffolds for tissue engineering, yet the limitation in material choice remains a barrier to clinical translation. Herein, a series of poly(propylene fumarate-co-propylene succinate) were synthesized using both one-pot and sequential ring-opening copolymerization reactions. Continuous liquid interface production-based photochemical 3D printing utilizing thiol-ene chemistry was used to fabricate precise structures with improved build time over the traditional poly(propylene fumarate)/diethyl fumarate 3D printing processes. Significantly, the materials do not exhibit a yield point under tension and Young's modulus of the 3D printed products can be tuned by more than 2 orders of magnitude (0.6-110 MPa) using polymer composition and the degree of polymerization. Printed constructs degrade fully under hydrolytic conditions and degradation rates can be tailored using polymer composition, polymer sequence, and resin formulation.

A Facile and Cost-Effective Method to Prepare Biodegradable Poly(ester urethane)s with Ordered Aliphatic Hard-Segments for Promising Medical Application as Long-Term Implants.

The article below describes a simple methodology to prepare cost-effective biodegradable poly(ester urethane)s (PEUs) with ordered hard segments (OHS) for medical application as long-term implants. A low-cost diurethane diol (1,4-butanediol-hexanediisocyanate-1,4-butanediol, BHB) was first designed and synthesized. Consequently, the BHB was employed as a chain extender to react with NCO-terminated poly(ε-caprolactone) to obtain PEUs. The molecular structural formats for BHB and PEUs were defined through NMR, FT-IR, and MS together with GPC, while the influence of OHS content on physical/chemical features for casted PEU films was investigated. The introduction of OHS could contribute to forming denser hydrogen-bonds, and consequently produce a compact network structure, resulting in great tensile capacity, low water absorption, and slow hydrolytic degradation rate by PEU films. PEU-2.0 films, which possessed the highest OHS content within PEUs, exhibited 40.6 MPa tensile strength together with 477% elongation at break, 4.3 wt % equilibrium water absorption and only 29.5% weight loss post-12 months’ degradation. In addition, cytotoxicity analysis of film extracts indicated that the cell viability of all PEUs containing OHS exceeded 75%, indicating good cytocompatibility. Due to outstanding tensile features, high biostability, nontoxic and absorbable degradation products and acceptable cytocompatibility, the cost-effective materials exhibited promising applications in the field of long-term implants.

Crystallization Behavior and Electrical Properties of Nanoparticle-Reinforced Poly(lactic Acid)-Based Films.

Graphene oxide (GO) and multiwalled carbon nanotubes with silver particles (MWNT-Ag) of different concentrations were used as nanofillers to prepare poly(lactic acid) (PLA) nanoparticle films through the solvent casting method. In this study, the effects of nanoparticles on the crystallization behavior, relationships between the dispersion and electrical properties, and hydrolytic degradation behaviors were investigated for the PLA/MWNT-Ag and PLA/rGO films. Differential scanning calorimetry was used to evaluate the crystallization behaviors of the PLA/MWNT-Ag and PLA/reduced GO (rGO) films. Electron probe microanalysis was performed to characterize the dispersion of MWNT-Ag, and X-ray diffraction and Raman spectroscopy were used to determine the degree of dispersion of rGO in the PLA matrix. The results showed that nanoparticles enhanced the crystallization kinetics of PLA as well as the hydrolytic degradation rate. From the measurement of electrical properties, the electrical conductivity of PLA/MWNT-Ag 1.0 wt% was much higher than that of the pure PLA and PLA/rGO films, showing that MANT and Ag nanoparticles contribute greatly to enhancing the electrical conductivity of the PLA/MWNT-Ag films.

Facile control of the surface property and hydrolytic degradation of poly(l-lactide) materials by coating poly(l-lactide)-based triblock copolymers with hydrophilic or hydrophobic block

The hydrophilicity of poly(l-lactide) (PLLA) films was increased and decreased by coating with hydrophilic PLLA-b-poly(ethylene glycol)-b-PLLA and hydrophobic PLLA-b-polybutadiene-b-PLLA. The hydrolytic degradation rate was controllable by the hydrophilicity of coated polymers.

Crystallization and degradation behaviour of multiblock copolyester blends in Langmuir monolayers

Supporting the wound healing of soft tissues requires fixation devices becoming more elastic while degrading. To address this unmet need, we designed a blend of degradable multiblock copolymers, which is cross-linked by PLA stereocomplexation combining two soft segments differing substantially in their hydrolytic degradation rate. The degradation path and concomitant structural changes are predicted by Langmuir monolayer technique. The fast hydrolysis of one soft segment leads to a decrease of the total polymer mass at constant physical cross-linking density. The corresponding increase of the average spacing between the network nodes suggests the targeted increase of the blend’s flexibility.Graphic abstract

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.

Preparation and characterization of highly pH-sensitive biodegradable poly(ether-ester-urethane) and its potential application for drug delivery

The objective of this study is to offer a highly pH-sensitive biodegradable polyurethane for application as an intelligent drug delivery carrier. A new pyridinyl diol ((3-((2-(pyridin-4-yl)ethyl)thio) propane-1,2-diol, PyDH) was first synthesized via thiol-ene “click” reaction. Then, PyDH-based poly(ether-ester-urethane) (PEEU-Py) was designed and prepared through the condensation polymerization of PyDH diol, poly(ether-ester) diol and diisocyanate. The pendent pyridine groups and the polyester segments could endow the polymers with pH sensitivity and degradability, respectively. The bulk structures and physicochemical properties of PEEU-Py were characterized via1H NMR, FT-IR, GPC, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and tensile testing. The cast membranes exhibited a sharp transition of the equilibrium swelling ratio (ESR) at pH 8.5∼9.0, and ESR increases of more than twofold and eightfold at pH 1.5 relative to pH 7.4 and pH 12.0, respectively. In vitro drug release studies showed that the release efficiency from the membranes was increased with decreasing pH value. The pH-sensitive release behaviors were related mainly to the swelling ability, and the slow hydrolytic degradation rate of PEEU-Py membranes had minimal influence on it. In addition, the in vitro cytotoxicity was evaluated by an MTT assay with L929 fibroblasts, and a cell viability of more than 75 % indicated satisfactory cytocompatibility. All the results demonstrate the potential application of PEEU-Py as a biological on–off switch for drug carriers that is triggered by an external pH change.