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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.

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.

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.

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.

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.