Yiu-Jiuan Lin

Pilocarpine-loaded chitosan-PAA nanosuspension for ophthalmic delivery

Chitosan-poly(acrylic acid) (CS-PAA) nanoparticles, to be used as ophthalmic drug carrier, were successfully prepared using template polymerization of acrylic acid (AA) in a chitosan solution. When the polymerization was done at 70°C for 45 min with a CS/AA weight ratio of 1:1, the surface structure of the prepared nanoparticles was most stable with the smallest mean diameter (92.0±7.5 nm) and a stable zeta potential (25.5±2.6 mV) in a buffer solution (pH 4.5). The size of the nanoparticles dramatically increased with the pH value of the medium. Both in vitro and in vivo studies revealed that the prepared nanoparticle suspension was better at sustaining the release of pilocarpine than either simulated tear fluid or commercial eye drops.

High Strength and Low Friction of a PAA-Alginate-Silica Hydrogel as Potential Material for Artificial Soft Tissues

In this study, a series of poly(acrylic) acid (PAA)-based hydrogels was prepared by UV polymerization. Hydrogels with an interpenetrating network structure were formed by combining PAA and alginate (Alg) solutions. The incorporation of nano-silica into these gel solutions significantly increased their compressive strength and fracture toughness but lowered their cross-linking density and friction coefficient. The prepared hydrogels were considerably hydrophilic for water content greater than 98%, which is in accordance with the nature of soft tissues such as cartilage. The preliminary cell culture of adipose stem cells (ADSCs) on PAA-Alg-Si hydrogels results in good biological safety. These features suggest that the PAA-Alg-Si hydrogels prepared in this study can be used as artificial soft tissues.

Stimulation of wound healing by PU/hydrogel composites containing fibroblast growth factor-2

In this study, polyurethane (PU)/hydrogel composites were fabricated for wound healing applications. The hydrogel is a copolymer of thermosensitive N-isopropyl acrylamide (NIPAAm) and acrylic acid (AAc). γ-ray irradiation was employed to simultaneously copolymerize NIPAAm with AAc and graft the hydrogel onto porous PU. Fibroblast growth factor-2 (FGF-2) was incorporated into the composite to facilitate wound healing. The physical properties of the composites were characterized, the in vitro release of FGF-2 was examined, and in vivo tests were conducted. The results indicate that the thermosensitive hydrogel can absorb most of the wound exudates due to its high water uptake ability. Due to its thermosensitive properties, the PU/hydrogel composite is easier to strip off than that of commercial wound dressing, which prevents additional injury to the wound when replacing the wound dressing. In vivo results show that the PU/hydrogel composite incorporating FGF-2 could accelerate wound healing and reduce scar formation.

A Novel In-Situ-Gelling Liquid Suppository for Site-Targeting Delivery of Anti-Colorectal Cancer Drugs

In order to avoid anti-cancer drugs undergoing a first-pass effect and reduce their toxicity, and to solve conventional suppositories defects, we developed an in-situ-gelling and injectable Pluronic–poly(acrylic acid) (Pluronic–PAA) liquid suppository, which could gel fast in the physiological state and had suitable gel strength and bioadhesive force. The liquid suppositories were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum for at least 6 h and while releasing the drug. The toxicity and cytotoxic tests indicated that Pluronic and PAA were non-toxic materials and could inhibit colon cancer cells when oxaliplatin was incorporated. C max and AUC0→12h values of oxaliplatin after rectal administration of a oxaliplatin suppository were higher than those for an oxaliplatin solution administered orally. These results suggest that an in-situ-gelling and injectable liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.

pH-Sensitive Hollow Alginate-Chitosan Hydrogel Beads for Bitter Gourd Delivery

Chitosan-alginate hydrogel beads with hollow structure were successfully prepared by dropping method for controlling delivery of bitter gourd (BG). Loading efficiency and loading content of the beads are 97.8% and 86.4%, respectively. Swelling accompanied with degradation behavior suggests the beads have pH-sensitive characteristics. In vitro release study reveals that the release behavior of these beads is environmental oriented. The MTS test demonstrates the hydrogel beads have good cytocompatibility and do not compromise cell viability. Finally, in vivo study confirms that hollow hydrogel beads have controlled and sustained release capability.

Poly(acrylic acid)–chitosan–silica hydrogels carrying platelet gels for bone defect repair

Most hydrogels derived from either natural or synthetic sources suffer from the lack of mechanical strength. In this study, high strength poly(acrylic acid)-chitosan-silica (PAA-Ch-Si) hydrogels were prepared by UV polymerization for tissue engineering applications. Compressive strength up to 42 MPa can be achieved by the formation of an interpenetrating network (IPN) structure between PAA and chitosan with nano-silica as the filler. The preliminary cell culture of osteoblast cells (7F2) on PAA-Ch-Si hydrogels indicates good biological safety. The growth factor (platelet glue) is fast and completely released from PAA-Ch-Si hydrogel scaffolds within 620 min. The scaffold starts to degrade after eight months in vitro. Histological examinations demonstrate that the hydrogel incorporated with growth factors and osteoblast cells can promote cell migration. All these results illustrate that PAA-Ch-Si hydrogels are beneficial for tissue engineering applications and can be used as scaffolds for bone defect repair.

High pH tolerance of a chitosan-PAA nanosuspension for ophthalmic delivery of pilocarpine.

In this paper, nanoparticles composed of chitosan (CS) and poly(acrylic acid) (PAA) were prepared by template polymerization for use as ophthalmic drug carrier. Before the polymerization, hydrogen peroxide was used to cut down the molecular weight of chitosan to improve its solubility and tolerance of pH values in the physiological condition. We found that, as the hydrogen peroxide concentration increased up to 2 M, the reaction temperature was kept at 60°C and depolymerization for 2 h, the molecular weight of chitosan was cut down to 4.1 × 104 and its pH tolerance was increased up to 7.1. The modified chitosan (MCS) is expected to tolerate in neutral condition without any precipitation. MCS–PAA nanoparticles for use as an ophthalmic drug carrier were successfully prepared using template polymerization of acrylic acid in the modified chitosan solution. The particle size of the nanoparticles was significantly affected by the pH value of the medium. Both in vitro and in vivo studies reveal that the prepared nanoparticles either modified or unmodified have the better ability in sustaining the release of pilocarpine than the simulated tear fluid and commercial eye drops.

Treating allergic conjunctivitis using in situ polyelectrolyte gelling systems

We prepared 0.3% Carbopol/15.5% Pluronic and 0.1% Alginate/15.5% Pluronic solutions as the in situ gelling vehicles for ophthalmic drug delivery of cromolyn. The flow properties, in vitro release and in vivo pharmacological response of these polyelectrolyte solutions and of commercial eye drops were evaluated and compared. The polyelectrolyte solutions were free-flowing at pH 4.0 and 25°C, and they turned to strong gels at pH 7.4 and 37°C due to the in situ phase transition. The in vitro release and in vivo pharmacological response indicated that both vehicles retained cromolyn better than the commercial eye drops. The results demonstrated that both systems are usable as in situ gelling vehicles to increase ocular therapeutic efficacy in treating allergic conjunctivitis.

Glycol chitin/PAA hydrogel composite incorporated bio-functionalized PLGA microspheres intended for sustained release of anticancer drug through intratumoral injection

Abstract A novel anti-hepatoma drug release hybrid system is prepared by using poly(acrylic acid) (PAA) and glycol chitin as substrate in combination with Paclitaxel (PTX)-loaded bio-biofunctionalized poly(lactic-co-glycolic acid) (PLGA) micro-particles, which is intended for cancer therapy through intratumoral injection. The rheological behavior of glycol chitin (7 wt%)/PAA illustrates that it has low gelling temperature (i.e. 17 °C at pH 7.56) which ensures that the formulation turns to gel at physiological condition. The gelling time of glycol chitin/PAA is 16 minutes at 25 °C and 3 minutes at 37 °C, which is convenient for doctors to inject the in-situ gel formulations into the tumor location of patient. The drug release behavior reveals that the system can dramatically postpone the drug release. The cell viability test indicates that the micro-particles with drug still have 62% inhibitory effect on hepatoma cells in the fourteenth day after combing with hydrogel. This system is a promising approach for cancer therapy through intratumoral injection of in-situ gel formulations to extend retention time at tumor sites.

Novel Formable PVA-Based Gel as a Potential for Atopic Dermatitis Treatment

The current commercial ointment for atopic dermatitis treatment not only has a low moisture retention capacity but also a highly percentage of having recrudescence. In this study, a novel formable polyvinyl alcohol (PVA) gel was developed. The gel takes 30 min to form a membrane. The membrane has high water vapor transmission rate and its moisturizing ability to skin is increased by adding humectants. It inhibits Staphylococcus aureus from growing and does not irritate to the skin, calf, and arms. Animal test supports that the gel membrane incorporated with tacrolimus truly palliates symptoms of skin inflammation and itch.