Transdermal delivery is one of the most convenient drug administration routes. In this study, the cellulose acetate membranes were cast with acetone as a solvent at 22 and 40℃. Polyethylene glycol (PEG, MW 600) was used as a pore-forming agent. The in vitro release rates of scopolamine base as a model drug through the membranes were evaluated in phosphate buffer solution (PBS, pH 7.4) at 32℃. The membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal mechanical analysis (TMA) and thermogravimetric analysis (TGA). It was observed that the drug permeation through the cellulose acetate membranes was obviously affected by the incorporated PEG content and formed membrane morphology. There was no drug flux from the cellulose acetate membranes prepared without PEG. An increased PEG content resulted in a faster scopolamine release due to a more porous structure created. Both the membrane fabrication temperature and the PEG content can affect the thermal, mechanical and morphological properties of the resultant membranes. With the optimized fabrication conditions, linear in vitro release profiles of scopolamine over 3 days were achieved. The membranes developed would be useful for transdermal delivery of drugs.

A method was developed to prepare thermosensitive poly (N-isopropylacrylamide) (PNIPAAm) hydrogels with an interpenetrating polymer network (IPN) structure for the purpose of improving its mechanical properties, response rate to temperature and sustained release of drugs. Although the differential scanning calorimetry data exhibited similarly lower critical solution temperature (LCST) between IPN-and non-IPN-PNIPAAm hydrogels, an increase in the glass transition temperature (Tg) ofthe IPNs relative to the normal PNIPAAm hydrogel was observed. In addition, the mechanical properties ofthe IPNs were greatly improved when compared with the normal PNIPAAm hydrogel. The interior morphology ofthe IPN-PNIPAAm hydrogels was revealed by scanning electron microscopy (SEM); the IPN hydrogels showed a fibrillar-like porous network structure that normal PNIPAAm did not have. Furthermore, by measuring the temperature dependence ofthe swelling ratio and deswelling kinetics, these IPN hydrogels also exhibited improved intelligent characteristics (e.g., controllable faster response rate) that depended on the composition ratio of the two network components. From the applications viewpoint, the effects of a shrinking-reswelling cycle around the LCST on the properties ofthe IPN hydrogels were examined to determine ifthese properties would be stable for potential applications. Bovine serum albumin was chosen as the model protein for examining its release from the IPNs at different temperatures. The release data suggested that an improved controlled release could be achieved by the IPN-PNIPAAm hydrogels without losing their intelligent properties.

A crown ether derivative (4′-allyldibenzo-18-crown-6, CE) was covalently incorporated into the network of temperature sensitive poly (Nisopropylacrylamide) (PNIPA) hydrogels by copolymerization in a mixed solvent of water and tetrahydrofuran (H2O/THF). The poly(Nisopropylacrylamide-co-4′-allyldibenzo-18-crown-6) (poly(NIPA-co-CE)) hydrogels exhibited dramatically faster deswelling rates than normal PNIPA hydrogels at a temperature (50℃) above their lower critical solution temperatures. The effect of the solvent component ratio in the mixed solvent during the copolymerization on the swelling properties of the poly (NIPA-co-CE) hydrogel was investigated. The thermosensitive poly (NIPA-co-CE) hydrogels have potential applications in the extraction of cations and separation of chiral drugs.

The model drug, 5-fluorouracil (5-FU) was loaded into the poly (N-isopropylacrylamide) (PNIPA) hydrogel at 25℃, then the drug-loaded, swollen hydrogel sample was carefully enveloped in the dialysis bag to form a novel thermo-responsive drug delivery system (DDS). The concentration of released 5-FU was monitored at 266 nm on the UV spectrophotometer. We found that this novel DDS provides a positive drug release pattern and the drug, 5-FU, was released faster at the increased temperature (37℃, 25℃) than the one at the decreased temperature (10℃<25℃). This was attributed to the double control of the thermo-sensitivity of the hydrogel matrix and the dialysis membrane. By employing the fast response PNIPA hydrogel instead of the conventional hydrogel in this novel DDS, we can further control the drug release rate and/or drug release amount etc., without changing the positive, thermo-responsive drug release pattern.

A method was developed to prepare thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with an interpenetratingpolymer network (IPN) structure for the purpose of improving its mechanical properties, response rate to temperature andsustained release of drugs. Although the differential scanning calorimetry data exhibited similarly lower critical solution temperature(LCST) between IPN- and non-IPN–PNIPAAm hydrogels, an increase in the glass transition temperature (Tg) ofthe IPNs relativeto the normal PNIPAAm hydrogel was observed. In addition, the mechanical properties ofthe IPNs were greatly improved whencompared with the normal PNIPAAm hydrogel. The interior morphology ofthe IPN–PNIPAAm hydrogels was revealed byscanning electron microscopy (SEM); the IPN hydrogels showed a fibrillar-like porous network structure that normal PNIPAAmdid not have. Furthermore, by measuring the temperature dependence ofthe swelling ratio and deswelling kinetics, these IPNhydrogels also exhibited improved intelligent characteristics (e.g., controllable faster response rate) that depended on thecomposition ratio of the two network components. From the applications viewpoint, the effects of a shrinking–reswelling cyclearound the LCST on the properties ofthe IPN hydrogels were examined to determine ifthese properties would be stable forpotential applications. Bovine serum albumin was chosen as the model protein for examining its release from the IPNs at differenttemperatures. The release data suggested that an improved controlled release could be achieved by the IPN–PNIPAAm hydrogelswithout losing their intelligent properties.

The objective of the study is to impart temperature and pH-sensitive capabilities to polysaccharide-based hydrogels, so that theycan change their swelling property upon external stimulation like temperature or/and pH. Dextran was chosen as the modelpolysaccharide compound for such a demonstration. A novel class of dextran-maleic anhydride (Dex-MA)/poly(Nisopropylacrylamide) hybrid hydrogels was designed and synthesized by UV photocrosslinking. The dextran-based precursor (Dex-MA) was prepared by substitutingthe hydroxyl groups in Dex by MA. This Dex-MA precursor was then photocrosslinkedwith a known temperature sensitive precursor (N-isopropylacrylamide, NIPAAm) to form hybrid hydrogels having a wide range ofcomposition ratio of Dex-MA to NIPAAm precursors. Due to the biodegradable nature of dextran, these Dex-MA/PNIPAAmhybrid hydrogels are partially biodegradable. These smart hybrid hydrogels were characterized by Fourier transform infraredspectroscopy for structural determination, differential scanningcalorimertry for thermal property, maximum swellingratio, swellingkinetics, temperature response kinetics, and effect of pH. The data obtained clearly show that these new smart hybrid hydrogels wereresponsive to the external changes of temperature as well as pH. The magnitude of smart and hydrogel properties of these hybridhydrogels were found to depend on the feed composition ratio of the two precursors. By changing the composition ratio of these twoprecursors, the phase transition temperature (lower critical solution temperature) of the hybrid hydrogels could also be adjusted tobe or near the body temperature for the potential applications in bioengineering and biotechnology fields.

Macroporous temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels have beensuccessfully synthesized by using poly(ethylene glycol) (PEG) as the pore-forming agent. Scanning electronmicroscope graphs reveal that the macroporous network structure of the hydrogels can be adjusted byapplying different molecular weights of PEG during the polymerization reaction. The surface roughnessof the hydrogels is also investigated using atomic force microscopy, and the results indicate that the surfaceof the PEG-modified gel is much rougher compared to that of the conventional PNIPAAm gel. The newlyinvented macroporous hydrogels exhibit much better properties as temperature-sensitive intelligentpolymers. For instance, at a temperature below the lower critical solution temperature (LCST), theyabsorb larger amounts of water and show obviously higher equilibrated swelling ratios in the aqueousmedium. Particularly, due to their unique macroporous structure, the PEG-modified hydrogels show atremendously faster response to the external temperature changes during deswelling and reswellingprocesses as the temperature cycles across the LCST. They can also shrink and lose water with dramaticallyrapid rates at temperatures above the LCST. The macroporous PNIPAAm gel has potential applicationsin controlled release of macromolecular active agents.Macroporous temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels have beensuccessfully synthesized by using poly(ethylene glycol) (PEG) as the pore-forming agent. Scanning electronmicroscope graphs reveal that the macroporous network structure of the hydrogels can be adjusted byapplying different molecular weights of PEG during the polymerization reaction. The surface roughnessof the hydrogels is also investigated using atomic force microscopy, and the results indicate that the surfaceof the PEG-modified gel is much rougher compared to that of the conventional PNIPAAm gel. The newlyinvented macroporous hydrogels exhibit much better properties as temperature-sensitive intelligentpolymers. For instance, at a temperature below the lower critical solution temperature (LCST), theyabsorb larger amounts of water and show obviously higher equilibrated swelling ratios in the aqueousmedium. Particularly, due to their unique macroporous structure, the PEG-modified hydrogels show atremendously faster response to the external temperature changes during deswelling and reswellingprocesses as the temperature cycles across the LCST. They can also shrink and lose water with dramaticallyrapid rates at temperatures above the LCST. The macroporous PNIPAAm gel has potential applicationsin controlled release of macromolecular active agents.

We have demonstrated a new strategy for preparing poly (N-isopropylacrylamide) (PNIPAAm) gel with significantly improved properties by polymerization-crosslinking in organic solvent (dimethyl sulfoxide, DMSO) and at low temperatures (0.5 and -22℃, below the melting point of DMSO). The effects of different synthesis conditions, including monomer concentration and polymerization temperature, on the formation of the PNIPAAm gels in DMSO were investigated. The properties of the resulting cryo-PNIPAAm gels were characterized by scanning electron microscopy (SEM) to reveal their interior morphology as well as the temperature dependence of the equilibrium swelling ratio, shrinking and swelling kinetics in water and their oscillatory shrinking-swelling kinetics over 3 min temperature cycles between 26 and 37℃. The SEM micrographs reveal that the interior microstructures of the cryo-PNIPAAm gels are very different from conventional PNIPAAm gels, and are much more regular and oriented than the conventional gels. This unique interior morphology of the cryo-PNIPAAm gels is believed to be responsible for the improved swelling and deswelling kinetics and excellent dynamic response without loss of water retention upon temperature cycling.

In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(ecaprolactone)(PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolongedand sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperaturesensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized byscanning electron microscopy (SEM), differential scanning calorimetry (DSC), and compression modulus measurements toinvestigate the morphological, thermal, and mechanical properties. The temperature dependence of swelling ratio and responsekinetics upon heating or cooling were also investigated to understand the smart properties, i.e., temperature sensitive properties ofthese DDSs. Finally, ovalbumin (OVA), used as the model drug, was loaded into PGCL-based microspheres to examine andcompare the effects of controlled release at different temperature (22 and 37 1C) of these novel smart DDSs.

In this paper, a P (NIPAAm-co-AAc) hydrogel with rapid temperature sensitivity and improved oscillatory properties over small temperature cycles around the physiologic temperature of 37℃ was synthesized in an alkaline solution (Tris/HCl solution, pH 8.8 and I=0.5M). SEM micrographs revealed that the unique properties achieved can be attributed to the expanded network structure generated in the alkaline solution during the copolymerization reaction. As a result of the dissociation of the carboxyl groups (-COOH) of AAc to carboxylate anions (-COO-), the electrostatic repulsion between carboxylate anions was strong and led to the expanded conformations of polymer chains. Therefore, the network of the hydrogels thus obtained was extremely expanded and exhibited fast temperature sensitivity and improved oscillating swelling-deswelling properties.