Jeong Ok Lim

Novel microencapsulation of potential drugs with low molecular weight and high hydrophilicity: hydrogen peroxide as a candidate compound.

Microencapsulation of drugs into solid biodegradable polymeric microspheres via solvent evaporation technique remains challenging especially with those having low molecular weight and high hydrophilicity nature. This paper presents an efficient encapsulation protocol for this group of drugs, demonstrated using hydrogen peroxide as a model compound that is encapsulated into poly(lactic-co-glycolic acid) microspheres. Hydrogen peroxide can be employed as antiseptic agent or its decomposed form into oxygen can be useful in various pharmaceutical applications. The new encapsulation technique was developed based on the modification of conventional double emulsion and solvent evaporation protocol with a backward concentration gradient of hydrogen peroxide. This was achieved by adding and controlling the concentration of hydrogen peroxide at the continuous phase during the solidification stage of the microspheres. Parameters involved in the production and the formulation aspect were optimized to achieve the best protocol having controlled efficiency of encapsulation that is simple, safe, practical, and economical. Evaluation on the encapsulation efficiency and the release profile has been made indirectly by monitoring the dissolved oxygen level of the solution where the microspheres were incubated. Morphology of the microspheres was investigated using scanning electron microscopy. This proposed method has successfully used to prepare batches of microspheres having different encapsulation efficiencies and its potential applications have been demonstrated accordingly.

OXIDANT EFFECTS ON POLYPYRROLE AND POLYANILINE SENSOR FOR SEVERAL VOLATILE ORGANIC GASES

Abstract The properties of polypyrrole and polyaniline sensor made from chemical polymerization were investigated. It was found that the oxidant (ammonium persulfate) affected solubility, conductivity and the sensing characteristics of polypyrrole and polyaniline. Atomic force microscopy (AFM) was used to investigate the morphology of the sensing films. A sensor array with 6 sensors was developed to recognize various kinds and quantities of volatile organic compounds (VOCs), such as benzene, toluene and chloroform. Principal Components Analysis (PCA) was used to analyze the VOC sensing characteristics.

An enzyme-modulated oxygen-producing micro-system for regenerative therapeutics

This study suggests the idea of treating oxygen as a drug in a biological environment and demonstrates that it will exhibit a dosage-dependent trend. To accomplish this, a micro-system was fabricated, having hydrogen peroxide as the oxygen-generating source, which was decomposed using catalase, a common enzyme found in nearly all living organisms. The relevance of the proposed micro-system was justified using cell viability assays under well-controlled and fixed conditions. This study was performed under two controlled conditions, normoxia and hypoxia, and tests were carried out using three different configurations of samples under each condition: direct addition of H(2)O(2), H(2)O(2) encapsulated with single layer, and H(2)O(2) encapsulated with double layers. This study demonstrates that the elegantly designed micro-system managed to control the decomposition of H(2)O(2) and avoided direct contact with cells, while also maintaining cell viability under a low oxygen environment.

In Vivo study of a blended hydrogel composed of pluronic F-127-alginate-hyaluronic acid for its cell injection application

The epitome that cell carrier serves solely as passive vehicles has become outdated. It is now evident that the carrier microenvironment also contributes in the regeneration process. In this study, a combination of alginate, pluronic F127 and extracellular matrix (ECM) component, hyaluronic acid (HA) based scaffold has been prepared for in situ gelling vehicles for muscle cells. ECM incorporated blended hydrogel showed enhanced uniform distribution of muscle cells in a nude mouse model forming the scaffold in situ allowed the muscle cells to proliferate efficiently, indicating that a pluronic F127/alginate/HA matrix provided a beneficial environment for cellular growth and expansion. The formation of gel beneath the skin of nude mice was confirmed using optical coherence tomography (OCT). OCT has been used to visualize the in situ localization of cells as well. This in situ gelation is found to be advantageous for regenerative applications due to the absence of toxic solvents or co-polymerization agents; besides the handling process is simple. This study demonstrates that an in situ blended hydrogels enables the favorable settlement of cells and satisfactory cell delivery for muscle regeneration applications.

Reduction of Allodynia by Intrathecal Transplantation of Microencapsulated Porcine Chromaffin Cells

Bovine chromaffin cells (BCCs) are well known to have analgesic effect to reduce acute or chronic pain when transplanted in the subarachnoid space and have been considered as an alternative therapy for pain management. However, due to recent concerns over risks associated with prion transmission, porcine tissue is considered to be an alternate xenogeneic source for clinical use. In the present study, we investigated whether microencapsulated porcine adrenal medullary chromaffin cells (PCCs) also have analgesic effect to reduce allodynia caused by neuropathic pain in chronic constriction injury model of rat. PCCs were isolated from a porcine adrenal medulla and then microencapsulated with alginate and poly. In in vitro tests, the microencapsulated PCCs were investigated whether they have an ability to release catecholamines responding to nicotine stimulation. The levels of catecholamines released from the microencapsulated PCCs were significantly higher than from microencapsulated BCCs. In addition, the microencapsulated PCCs released catecholamines and met-enkephalin responding to cerebral spinal fluid (CSF) retrieved from a neuropathic pain model. In in vivo tests, implantation of microencapsulated PCCs reduced both mechanical and cold allodynia in chronic constriction injury model of a rat whereas the microencapsulated BCCs reduced only cold allodynia under the same conditions. The injection of antagonist of opioid peptides reversed the reduction of cold allodynia in microencapsulated PCC-received animal. The levels of catecholamines in the CSF of rats after implantation of microencapsulated PCCs were significantly higher than in the control group. These data suggest that microencapsulated PCCs may be another effective source for the treatment of neuropathic pain.

Polypyrrole-coated woven fabric as a flexible surface-heating element

AbtractPolypyrrole (PPy) was coated sequentially by chemical and electrochemical methods on a woven fabric, giving rise to a fabric having high electrical conductivity. We investigated the effects of the preparation conditions on the various properties of the resulting fabric. The PPy-coated fabric with optimum properties was obtained when it was prepared sequentially by chemical polymerization at the elevated temperature of 100 °C under a pressure of 0.9 kgf/cm2 and then electrochemical polymerization with a 3.06 mA/cm2 current density at 25 °C for 2 hrs with the separator plate. The surface resistivity of the resulting fabric was as low as 5Ω/□.The PPy-coated fabric prepared under the optimum conditions showed practically applicable heat generating property. When electrical power was supplied to the fabric using a commercial battery for a mobile phone (3.6 V, LGL1-AHM), the temperature of the fabric increased very quickly from room temperature to ca. 55 °C within 2 min and was maintained for ca. 80 min at that temperature. The heat generating property of the fabric was extremely stable, exhibiting similar behavior over 10 repeated cycles. Therefore, we suggest that the PPy-coated fabric in this study may be practically useful for many applications, including flexible, portable surface-heating elements for medical or other applications.

Controlled release of oxygen from PLGA-alginate layered matrix and its in vitro characterization on the viability of muscle cells under hypoxic environment

Coagulative necrosis often occurs under hypoxic conditions, causing major limitation in the field of tissue engineering especially those dealing with larger tissues and organs. In this study, a comprehensive work has been performed in developing a tailor made design of a dual layered matrix that can produce oxygen to be utilized in tissue engineering application. Optimizations of protocol, ingredient and condition of the system were carried out specifically based on the responses observed from in vitro studies using L6 rat skeletal muscle cell as a candidate. Oxygen was generated from decomposition of encapsulated hydrogen peroxide. Poly (D,L)-lactide-co-glycolide (PLGA) with molecular weights of 90,000 and 110,000 gmol−1 managed to secure good encapsulation of hydrogen peroxide for this application, while the best stirring time during the encapsulation was found to be 8 hours. The PLGA microspheres were coated with a secondary layer of alginate that was pre-grafted with calatase to form the dual layer system. This dual layered architecture has successfully controlled the release rate of oxygen at an optimum level for the survival of muscle cells under hypoxia condition. It was found that muscle cells have low tolerance limit towards the direct contact with hydrogen peroxide, however the cells maintained high viability within encapsulated hydrogen peroxide in the matrix system. It was observed that 4% of encapsulated hydrogen peroxide in the matrix system can produce efficient amount of oxygen at a controlled release manner to sustain the survival of muscle cells under hypoxic condition.

Enhanced Transdermal Delivery of Local Anesthetics by Liposome Formulation of Local Anesthetic Mixture

Various concentrations of either lidocaine or tetracaine, plus combinations of lidocaine and tetracaine were formulated into liposomes to improve topical anesthesia. The topical anesthetic effects of these liposomal mixtures of local anesthetics (Lipo-MLA) were then compared with those of EMLA (Eutectic Mixture of Local Anesthetics) and single local anesthetic liposomes using a pinprick test on healthy adult volunteers. The Lipo-MLA exhibited significantly improved anesthetic effects compared to the EMLA and single local anesthetic liposomes with a faster onset time of approximately thirty minutes and duration of at least four hours. A dermal toxicity study using rats revealed that Lipo-MLA was safe at greater than 2,000 mg/kg bodyweight.

Biocompatibility of Phema and P(Hema-Co-Sma) Hydrogels

To replace a poly(2-hydroxyethyl methacrylate) (PHEMA) sponge, which has limited applications as an implant material, PHEMA and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) (P(HEMA-co-SMA)) hydrogels with enhanced biocompatibility were prepared based on the copolymerization of 2-hydroxyethyl methacrylate (HEMA) and sodium methacrylate (SMA) at a high monomer concentration. When the cytotoxicity, cell adhesion, and in vivo tissue reaction of the resulting hydrogels were investigated, the results suggest that hydrogels prepared by the copolymerization of HEMA and SMA at a high monomer concentration have great potential as implant materials with an excellent biocompatibility.

Optimization of recombinant human platelet-derived growth factor-BB encapsulated in Poly (lactic-co-glycolic acid) microspheres for applications in wound healing

Growth factors play multiple and critical roles in wound repair processes. Platelet-derived growth factor (PDGF) is a potent growth factor that is particularly important in the early inflammatory phase of wound healing. In order to extend the half-life of PDGF, polymeric encapsulation is used. In the current study, Poly (lactic-co-glycolic acid) (PLGA) microspheres containing recombinant human (rh) PDGF-BB were prepared to prolong the effectiveness of this growth factor. PLGA microspheres were optimized using a modified w/o/w-double-emulsion/solvent evaporation method by changing the processing conditions of stirring speed and emulsifier (polyvinyl alcohol) concentration. Microspheres prepared using the optimized method released rhPDGF-BB for up to three weeks. An in vitro migration assay showed a significant decrease in the wound area in cells treated with rhPDGF-BB microspheres compared to control cells. These findings demonstrate the potential of rhPDGF-BB encapsulated in microspheres to enhance wound healing.