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Background: Cabazitaxel (CBZ) is a second-generation taxane that has the potential to overcome taxane-resistance due to the low affinity for the P-glycoprotein efflux pump. However, with the high systemic toxicity such as neutropenia and hypersensitivity, the clinical use is restricted to patients with metastatic castration-resistant prostate cancer who show progression after docetaxel-based chemotherapy. MPB-1734 is a CBZ nanoformulation which is currently being evaluated as monotherapy in patients with advanced solid tumors in a Phase 1/2a trial (NCT04643418). It is developed to overcome the limitations associated with CBZ application and as potential therapeutic agent for chemo-resistant cancers. This work outlines the results of preclinical studies that support the tumor targeting ability, improved safety profiles, significant therapeutic effect, and synergistic benefit in combination with immune checkpoint inhibitor. Methodology: A series of nonclinical studies of MPB-1734 were conducted including toxicology evaluations in two species and the antitumor activity evaluations in a range of xenograft mice models as cervical cancer (KB), ovarian cancer (OVCAR3) and platinum-resistant human ovarian cancer patient-derived-xenograft (PDX) model (OV0276). The antitumor activity of MPB1734 combined with anti-PD-1 antibody were also evaluated in the syngenetic 4T1 breast cancer mice model. Results: Toxicology evaluations of MPB-1734 demonstrated the safety profiles of CBZ were significantly improved, and the tolerated doses of MPB-1734 are at least 2 folds higher than commercial formulation. An in-vivo tumor targeting study showed that MPB1734 mainly accumulated in the tumor sites, rather than in the vital organs. MPB1734 exhibited a better efficacy compared to commercial formulation in KB and OVCAR3 models. For platinum-resistant PDX model, MPB-1734 demonstrated significant anti-tumor efficacy (TGI:100%, p compared to anti-PD-1 antibody monotherapy (TGI: 2.8%) and MPB-1734 monotherapy (TGI: 52.9%). This synergistic benefit may result from increased CD8+ T cells in tumor region after MPB-1734 treatment. Conclusion: MPB-1734 can reduce the major dose-limiting side effect (neutropenia) of CBZ and increase the tolerated dose. With tumor targeting ability, superior antitumor effects were demonstrated as compared with commercial formulation in a range of cancer models. MPB-1734 combined with anti-PD-1 antibody showed synergistic benefit in tumor inhibition. These preclinical results support the potential use of MPB-1734 as therapeutic agent for chemo-resistant cancer with monotherapy or combination therapy with immuno-oncology agents. Citation Format: Yuan Hung Hsu, Chih-Lung Chen, Jhih-Yun Jian, Ming-Cheng Wei, Wen-Yuan Hsieh, Chia-Wen Huang, Yung-Chu Chen, Tzu-Hsin Liao, Shian-Jy Wang. Preclinical studies of the cabazitaxel nanoformulation MPB-1734 support therapeutic application in chemo-resistant solid tumors and synergistic benefit in combination with immune checkpoint inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 818.

Flip chip ball grid array on strip (FCCSP) has been found in wide range such as telecommunication, computer, and workstation application because it provided solutions for high speed demand, high input/output (I/0) density, and high electrical performance requirement. Due to the trend of thinner and smaller of future PKG, the higher technology of assembly is required. High Band Width FCCSP (HBW) structure is the high-end product nowadays. This product is almost applied on mobile or pad, so total thickness will play an important role of end product’s total thickness. In conclusion, this experiment is to thin the thickness from 680um (include ball height) to be less than 500 or 400um based on HBW structure for customer’s future requirement.

In order to enhance visualization of soft tissues, a dual-imaging diagnostic polymersome system featured with highly hydrated multilamellar wall structure capable of simultaneously embedding a hydrophobic near-infrared fluorophore, Cy5.5, and a paramagnetic probe, gadolinium (Gd(III)) cations was developed. The polymersomes were obtained from the self-assembly of lipid-containing copolymer, poly(acrylic acid-co-distearin acrylate), in aqueous solution. The Cy5.5 and Gd(III) species were loaded into polymersomes via hydrophobic association (loading efficiency of Cy5.5 ca 74%) and electrostatic complexation (Gd(III) 83%), respectively. The Cy5.5/Gd(III)-loaded polymersomes (CGLPs) have shown excellent payload confinement, reduced dilution effect on assembly dissociation and decreased protein/salt-induced colloidal aggregation. Owing to the highly hydrated structure of vesicular membrane, the superior contrast enhancement of CGLPs in magnetic resonance (MR) imaging was obtained as a result of prolonged rotational correlation time of Gd(III) cations and fast water exchange from Gd(III) to bulk solution. The CGLPs exhibit a 15-fold higher longitudinal relaxivity value ( ca 60 mM −1 s −1 ) than that (4 mM −1 s −1 ) of the commercial contrast agent, Magnevist, in phosphate buffered saline. The in vivo characterization demonstrates that CGLPs exhibit a signal-to-noise ratio in T 1 -weighted MR image contrast similar to that of Magnevist, yet with a Gd dose 5-fold lower. An excellent contrast in NIR imaging at tumor site was attained following the intravenous injection of GGLPs into Tramp-C1 tumor-bearing mice (C57BL/6). Along with their non-toxicity at the dose used, these results demonstrate the great potential of the CGLPs as an advanced diagnostic nanodevice.

Polychloromethylstyrene (PCMS)-block-polystyrene (PS) copolymers were prepared by controlled free-radical polymerization in the presence of 2,2,6,6-tetramethylpiperidinooxy and 2,2′-azobisisobutyronitrile (AIBN) initiator. The PCMS-b-PS copolymers had narrow molecular weight distributions, and the block lengths were controlled by the reaction time and the molar ratios of chloromethylstyrene/AIBN and styrene/PCMS macroinitiator. The block copolymers were further quaternized with triethylamine. The amphiphilic cationic block copolymers formed colloidal particles; the effects of the pH value, salt concentration, and solvent polarity on the particle size were investigated with a dynamic light scattering analyzer. The average colloid size increased with increasing pH value and salt concentration. This implied that the colloid formed a protonated hydrophilic shell and hydrophobic styrene core in water. Furthermore, with the addition of tetrahydrofuran to the aqueous solution, the styrene segments in the core could be inverted to the outside of the colloid. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and various nonmalignant conditions. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In a previous study, it was demonstrated that the skin phototoxicity of meta-tetra(hydroxyphenyl)chlorin (m-THPC), a photosensitizer used in the clinic, can be significantly reduced after micellar encapsulation; however, no improvement in antitumor efficacy was observed. In this work, a folate-conjugated polymeric m-THPC delivery system is developed for improving tumor targeting of the photosensitizer, preventing photodamage to the healthy tissue, and increasing the effectiveness of the photosensitizers. The results demonstrate that folate-conjugated m-THPC-loaded micelles with particle sizes around 100 nm are taken up and accumulated by folate receptor-overexpressed KB cells in vitro and in vivo, and their PDT has no significant adverse effects on the body weight of mice. After an extended delivery time, a single dose of folate-conjugated m-THPC-loaded micelles has higher antitumor effects (tumor growth inhibition = 92%) through inhibition of cell proliferation and reduction of vessel density than free m-THPC or m-THPC-loaded micelles at an equivalent m-THPC concentration of 0.3 mg kg(-1) after irradiation. Furthermore, folate-conjugated m-THPC-loaded micelles at only 0.2 mg kg(-1) m-THPC have a similar antitumor efficacy to m-THPC or m-THPC-loaded micelles with the m-THPC concentration at 0.3 mg kg(-1) , which indicates that the folate conjugation on the micellar photosensitizer apparently reduces the requirement of m-THPC for PDT. Thus, folate-conjugated m-THPC-loaded micelles with improved selectivity via folate-folate receptor interactions have the potential to reduce, not only the skin photosensitivity, but also the drug dose requirement for clinical PDT.

A facile approach of forming stable polymeric complexes by the two-stage phase transition of the graft copolymer comprising poly(acrylic acid) (PAAc) as the backbone and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts in water was illustrated. Rather loose and hydrated polymeric aggregates with a characteristic hydrophobic multicore structure, achieved by the first-stage thermally induced phase transition of PNIPAAm grafts, underwent the core structure rearrangement (including multicore fragmentation and fusion) upon the second-stage dehydration of mPEG grafts at 90 °C. This was followed by hydrogen-bond pairings of mPEG and PNIPAAm chain segments with unionized AAc residues acting as an effective protective shell against potential hydration of the hydrophobic inner cores during the annealing process. The polymer complexes thus obtained show surprisingly enhanced hydrophobicity of inner cores at 25 °C in water and excellent stability of the morphological structure in response to the temperature disturbance.

Shell cross-linked (SCL) assemblies are prepared from the thermally induced three-layered, onion-like micelles of graft copolymers comprising acrylic acid (AAc) and 2-methacryloylethyl acrylate (MEA) as the backbone units and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts via radical polymerization of the MEA residues within the AAc-rich interfacial layers in the aqueous phase of pH 5.0 at 60 °C. The resulting nanosized SCL assemblies exhibit versatile structural regulations in a fully reversible manner in response to changes in pH and temperature. At 20 °C, SCL assemblies retain the morphology of vesicle-like hollow microspheres with pH-controlled water influx and particle size. At pH 7.0, SCL assemblies remain invariant in both vesicular structure and size irrespective of the temperature increase beyond the coil-to-globule phase transition of PNIPAAm grafts occurring primarily in a highly individual manner. When the temperature increases from 20 to 60 °C at pH 5.0, the hollow particle size is greatly reduced, accompanied by the development of hydrophobic, impermeable PNIPAAm lumens attached to the inside surfaces of the interfacial gel layers. In addition, SCL assemblies undergo a dramatic thermally induced transformation from the vesicle-like to micelle-like morphology by virtue of yielding hydrophobic PNIPAAm inner cores at pH 3.0. The thermally evolved morphology of SCL assemblies is governed by the vesicle structure in response to the effect of pH on the AAc ionization within the interfacial gel layers at ambient temperature.

Two graft copolymers comprising acrylic acid (AAc) and 2-methacryloylethyl acrylate (MEA) units as the backbone and either poly(N-isopropylacrylamide) (PNIPAAm) alone or both PNIPAAm and monomethoxypoly(ethylene glycol) (mPEG) as the grafts were synthesized. These copolymers in the aqueous phase (pH 5.0) underwent thermally induced self-assembly into micelles. For the copolymer containing PNIPAAm grafts only, extensive interactions between un-ionized AAc residues and PNIPAAm segments occurred, thereby rendering polymer backbones partially embedded within the hydrophobic cores of thermally induced micelles. This then led to bulk (core/shell) cross-linking of micelles upon radical polymerization of the MEA units within the micellar assemblies in the aqueous phase. By contrast, with mPEG being incorporated into the copolymer, association of the backbones with PNIPAAm is greatly retarded. As a result, three-layer onion-like polymeric micelles consisting of hydrophobic PNIPAAm cores surrounded by AAc-rich shel...

Significant second-moment transmission effects and obvious time-varying patterns of correlation coefficients among major equity and currency markets in the US, Japan and the UK are found to exist. Such observations inspire the time-varying setting of dynamic conditional correlation coefficients in MGARCH models. On the other hand, the multivariate Student-t distribution is suitable for analysing the visible leptokurtosis that is common in financial markets. Both are important for international portfolio risk management. Thus, a comparison on the hedging efficiency of hypothetical portfolios consisting of stock and currency future positions is conducted in order to justify the multivariate Student-t distribution based on the DCC-MGARCH model.

This study compares efficiencies of five Generalised Autoregressive Conditional Heteroskedasticity (GARCH) models in terms of value at risk (VaR) backtesting on the number of prediction failures and the average deviation between VaR and realized return series. Unlike the previous literature which presumes constant correlation coefficients, a new model proposed by Engle (2002, the DCC model) is applied to highlight time-varying conditional correlations amongst positions, which is essential for portfolio risk management. From the empirical studies of exchange rates data including the US Dollar to British Pound, Japanese Yen and Euro Dollar, we find that the DCC model produces least prediction failures.

This study presents a new radix-4 butterfly design for Viterbi decoders. The branch symmetry of the proposed radix-4 butterfly is exploited to design a low-complexity radix-4 butterfly module to simplify the implementation of the soft-decision Viterbi decoder. By exploiting the branch symmetry, only a half of branch metrics need to be computed, while other metrics can be derived from the computed branches. Therefore, the branch metric computation of the radix-4 butterfly can be reduced by a factor of 2. Considering the convolutional code in the DAB system as an example, experimental results indicate that the proposed radix-4 butterfly design can reduce the number of FPGA slices of the radix-4 butterfly module by 24% over the conventional design.

This article applies the dynamic conditional correlation model of Engle (2002) with error correction terms in order to investigate the optimal hedge ratios of British and Japanese currency futures markets. For a comparison, the estimates of three other models -- traditional generalized autoregressive conditional heteroskedasticity (GARCH), ordinary least square (OLS) and error correction model (ECM) -- are also reported. Results show that the dynamic conditional correlation model yields the best hedging performance in both futures markets. Nonetheless, the traditional multivariate GARCH model (which exhibits constant conditional correlations and time-varying hedge ratios) performs the worst hedging effectiveness, even inferior to the time-invariant hedging methods (OLS and ECM). The inclusion of dynamic conditional correlations in the GARCH model can therefore better capture the frequent fluctuations in futures markets.

Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i. v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen and kidney by 20.4%, 42.5% and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively.

The effects of SDS on the structural changes of the thermally induced polymeric micelles from a graft copolymer comprising poly(acrylic acid) (PAAc) as the backbone and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts in aqueous solution are studied. At low temperature, SDS micelles form via the hydrophobic association of SDS molecules with the PNIPAAm grafts at a critical aggregation concentration of SDS (cac(SDS)) much lower than its critical micelle concentration. Consequently, the critical aggregation temperature of the graft copolymer is elevated. The corresponding structure of the thermally induced polymeric micelles is characterized by an abrupt reduction in the particle size and an increased tendency toward formation of the monocore structure with a more compact and hydrophobic PNIPAAm microdomain being developed. On the other hand, upon the polymeric micelle formation at high temperature, the copolymer-bound SDS micelle structure is disrupted and the dissociated SDS molecules migrate to the core-shell interface with their alkyl chains residing in the liquidlike region of the hydrophobic PNIPAAm microdomain. The correlation between the polymeric particles and copolymer-bound micelles is further substantiated by showing the change of the colloidal particle size in response to changes in cac(SDS) via adjusting the pH of the aqueous copolymer/SDS solutions.

Graft copolymers comprising poly(acrylic acid) (PAAc) as the backbone and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts were prepared and characterized. These copolymers with the AAc residues in the negatively charged state underwent self-assembling into large polymeric aggregates in water in the range 32−35 °C due to the formation of the multicore structure (comprising several solidlike hydrophobic PNIPAAm cores surrounded by the liquidlike interfacial layers) and the intercore PEG connections. These rather labile intercore PEG connections were partially destroyed due to the continual dehydration and solidification of the liquidlike interfacial layers with increasing temperature, thereby leading to fragmentation of the original aggregates into smaller particles with the more distinct core/shell structure. The final particle size was virtually governed by the structure of the hydrophobic PNIPAAm microdomains in response to the effects of the PNIPAAm conce...

This paper explores optimal international asset allocation policies subjected to the equity holding constraint within an intertemporal framework. To deal with the co-existent realities of agents’ heterogeneous preferences and international market friction, the perturbation method is employed to derive approximate analytic solutions.

Dextran hydrogels were obtained by radical copolymerization of methacrylated dextran (MA-dextran) with acrylic acid (AAc) using ammonium peroxydisulfate (APS) and N,N,N′,N′-tetramethylethylenediamine (TMEDA) as an initiation system in an aqueous solution. The AAc content in hydrogels was determined by FTIR. Copolymerization of MA-dextran with AAc increased the cross-linking density of hydrogels by the bridging effect of AAc and, to a certain extent, facilitated the formation of hydrogels from MA-dextran with a low degree of MA substitution (DS). For hydrogels with a low DS (5.9), the swelling at pH 7.4 initially decreased and then increased with increasing AAc. The swelling of hydrogels with high DS (11.4 and 22.4) increased gradually with AAc. This discrepancy was explained by the differences in the chemical potentials of water outside and inside of the hydrogels as a function of AAc. Further increases of AAc, however, led to a reduction in polymerization conversion and even incomplete formation of hydrogel. The reduction in polymerization yield was primarily a consequence of the pH reduction and salt formation of AAc with TMEDA.

A copolymer of poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) was modified with a benzyl moiety and labeled with I-131. A micelle system, (131)I-benzyl-micelles, formed from (131)I-benzyl-PEG-PCL and PEG-PCL-PC, was created and used for in vitro characterization and in vivo evaluation. Administration of (131)I-benzyl-micelles to a colon carcinoma-bearing mouse model gives a 4.9-fold higher tumor-to-muscle ratio at 48 h post-injection than treatment with the unimer (131)I-benzyl-PEG-PCL. Scintigraphic imaging, biodistribution results and pharmacokinetical evaluation all demonstrated that (131)I-benzyl-micelles are a plausible radioactive surrogate for PEG-PCL copolymer micelles. Modifying the amphiphilic copolymer with a benzyl moiety and labeled it with iodine-131 should make possible the real-time and noninvasive evaluation of the pharmacokinetics of copolymer micelles in vivo.

Graft copolymer comprising acrylic acid (AAc) units as the backbone and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxy poly(ethylene glycol) (mPEG) as the grafts undergoes phase transition and supramolecular assembly into colloidal particles in water upon the thermally induced hydrophobic association. The structural characteristics of the polymeric assemblies made from the graft copolymer in water are strongly dependent on the copolymer concentration and the way that the copolymer solution is subjected to heating from 25 degrees C to the phase transition region (occurring in the range 30 approximately 35 degrees C). The resultant assemblies are characterized by forming hydrophobic PNIPAAm regions with the multicore architecture and intercore connections. Interesting enough, these colloidal systems obtained from the copolymer solutions at different concentrations (10.0 and 1.0 mg/mL) and heating methods (fast and slow heating) exhibit very different structural responses when subjected to further temperature increase (from 30 approximately 35 to 60 degrees C). The mutual interactions among the components (PAAc backbone and PNIPAAm and mPEG grafts) of the copolymer were shown to play a crucial role in the evolution of the ultimate assembly structure. A molecular packing model was proposed to illustrate the mechanisms of the thermally induced structural transformation processes for the amphiphilic graft copolymer in water.

The image fusion technique is to maximize the information in images at same area or object taken by different sensors. It enhances unapparent features at each image and wildly applied at remote sensing, medical image, machine vision, and military identification. In remote sensing, the latest sensors usually provide 11-bit panchromatic data which compose more radiometric information; however the standard visual equipment can only produce 8-bit resolution content that limits the analysis of imagery on the screen or paper. This paper shows how to preserve the original 11-bit information after the DRA (Dynamic Range Adjustment) approaches and keep the output from color distortion during the following pan/multi-spectrum image fusion process. We propose a good dynamic range compression method converting the original IKONOS panchromatic image into high, low luminance and typical linear stretched images and using wavelet fusion to enhance the radiometric visualization and keeping good correlation with the multi-spectrum images in order to produce fine pan-sharpened product.

Hsin-Hung Chen,1 Wen-Chia Huang,2 Wen-Hsuan Chiang,2 Te-I Liu,2 Ming-Yin Shen,2,3 Yuan-Hung Hsu,4 Sung-Chyr Lin,1 Hsin-Cheng Chiu2 1Department of Chemical Engineering, National Chung Hsing University, Taichung, 2Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 3Department of Surgery, National Taiwan University Hospital-Hsinchu Branch, 4Pharmaceutical Optimization Technology Division, Biomedical Technology and Device Research Laboratory, Industrial Technology Research Institute, Hsinchu, Taiwan Abstract: In this study, a novel pH-responsive cholesterol-PEG adduct-coated solid lipid nanoparticles (C-PEG-SLNs) carrying doxorubicin (DOX) capable of overcoming multidrug resistance (MDR) breast cancer cells is presented. The DOX-loaded SLNs have a mean hydrodynamic diameter of ~100nm and a low polydispersity index (under 0.20) with a high drug-loading efficiency ranging from 80.8% to 90.6%. The in vitro drug release profiles show that the DOX-loaded SLNs exhibit a pH-controlled drug release behavior with the maximum and minimum unloading percentages of 63.4% at pH 4.7 and 25.2% at pH 7.4, respectively. The DOX-loaded C-PEG-SLNs displayed a superior ability in inhibiting the proliferation of MCF-7/MDR cells. At a DOX concentration of 80 µM, the cell viabilities treated with C-PEG-SLNs were approximately one-third of the group treated with free DOX. The inhibition activity of C-PEG-SLNs could be attributed to the transport of C-PEG to cell membrane, leading to the change of the composition of the cell membrane and thus the inhibition of permeability glycoprotein activity. This hypothesis is supported by the confocal images showing the accumulation of DOX in the nuclei of cancer cells and the localization of C-PEG on the cell membranes. The results of in vivo study further demonstrated that the DOX delivered by the SLNs accumulates predominantly in tumor via enhanced permeability and retention effect, the enhanced passive tumor accumulation due to the loose intercellular junctions of endothelial cells lining inside blood vessels at tumor site, and the lack of lymphatic drainage. The growth of MCF-7/MDR xenografted tumor on Balb/c nude mice was inhibited to ~400mm3 in volume as compared with the free DOX treatment group, 1,140mm3, and the group treated with 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] solid lipid nanoparticles, 820mm3. Analysis of the body weight of nude mice and the histology of organs and tumor after the administration of DOX-loaded SLNs show that the SLNs have no observable side effects. These results indicate that the C-PEG-SLN is a promising platform for the delivery of therapeutic agents for MDR cancer chemotherapy. Keywords: pH-responsive, solid lipid nanoparticles, multidrug resistance, permeability glycoprotein

In this study, pH-responsive inulin hydrogels were prepared by radical copolymerization of methacrylated inulin (MA-inulin) with acrylic acid (AAc) in aqueous solution using ammonium peroxydisulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TMEDA) as an initiation system. The AAc content in hydrogels was evaluated by FTIR spectroscopy. The covalent bridging of AAc among MA moieties of MA-inulins was observed by a significant increase in the effective network density of hydrogels and further confirmed by TGA studies. While, at a low content of AAc, the hydration of hydrogels at pH 7.4 decreased owing to the increased crosslinking density, the swelling subsequently increased with further increasing AAc as a consequence of the increased ionic osmotic pressure within hydrogels. The change in swelling of hydrogels in response to pH change between 7.4 and 2.2 was therefore enlarged when the AAc content increased.