X-Message-Number: 32039
Date: Tue, 6 Oct 2009 20:27:24 -0700 (PDT)
From: 
Subject: could green tea polyphenol liposomes aid organ cryopreservati...


[Green tea polyphenols reduce cryopreservation related damage, but have such 
poor permeation characteristics that they are not suitable for use in whole 
organ cryopreservation. Liposome encapsulation of green tea polyphenols 
seemingly overcomes the permeation limitation, but it is not known whether such 
polyphenol loaded liposomes could offer significant protection against 
cryopreservation damage, over and above that provided by the liposomes 
themselves. Application of ultrasound can release the contents of liposomes, and
so may be used to "activate" polyphenol loaded liposomes by liberating their 
polyphenols, which then can act to reduce cryopreservation related damage 
throughout whole organ systems. Thus the combination of liposome encapsulation 
and ultrasound may enable green tea polyphenols to reduce whole organ 
cryopreservation related damage.]

Ann Biomed Eng. 2009 Sep 3. [Epub ahead of print]

A Mathematical Model of Drug Release from Liposomes by Low Frequency Ultrasound.

    Enden G, Schroeder A. Department of Biomedical Engineering, Ben-Gurion 
    University of the Negev, P.O. Box 653, Beer Sheva, 84105, Israel

    Administration of drugs using small (<100 nm) unilamellar liposomes enables 
    effective targeting of tumors and inflamed tissue. Therapeutic efficacy may 
    be enhanced by triggering liposomal drug release in the desired organ in a 
    controlled manner using a noninvasive external signal. Previous studies have
    demonstrated that low frequency ultrasound (LFUS) can be used to control 
    the release of drugs from liposomes. LFUS irradiation has a twofold effect: 
    (1) it causes the impermeable liposome membrane to become permeable and (2) 
    it induces liposome disintegration. Immediately upon cessation of LFUS 
    irradiation the membrane resumes its impermeable state and liposome 
    disintegration stops. The mathematical model presented here is aimed at 
    providing a better quantitative and qualitative understanding of 
    LFUS-induced liposomal drug release, which is essential for safe and 
    effective implementation of this technique. The time-dependent release 
    patterns are determined by the liposome disintegration patterns and by two 
    key parameters: (a) the average permeability of the membrane to the drug and
    (b) the ratio between the volume of the entire dispersion and the initial 
    volume of all the liposomes in the dispersion. The present model implies 
    that LFUS irradiation triggers two liposomal drug-release mechanisms: the 
    predominant one is diffusion through the LFUS-compromised liposome membrane,
    and the less significant one is liposome disintegration.
PMID: 19731036

Cell Transplant. 2009;18(5):513-9.
Long-term preservation of rat skin tissue by epigallocatechin-3-o-gallate.

    Kim H, Kawazoe T, Matsumura K, Suzuki S, Hyon SH. Department of Medical 
    Simulation Engineering, Research Center for Nano Medical Engineering, 
    Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, 
    Japan.

    Skin grafts can be preserved by cryopreservation and refrigerated storage at
    4 degrees C. Epigallocatechin-3-O-gallate (EGCG) enhances the viability of 
    stored skin grafts and also extends the storage time up to 7 weeks at 4 
    degrees C. EGCG, the major polyphenolic constituent present in green tea, 
    has potent antioxidant, antimicrobial, antiproliferative, and free radical 
    scavenging effects. This study examined the effects of EGCG on skin 
    cryopreservation. Skin sample biopsy specimens from GFP rats were previously
    treated with/without EGCG then moved to -196 degrees C. Skin samples were 
    transplanted to nude mice after 2, 8, and 24 weeks of preservation. Glucose 
    consumption was measured after thawing to assess the metabolic activity. Two
    weeks later the transplanted skin grafts were excised and histologically 
    analyzed. Histological examinations revealed the degeneration of the 
    epidermal and dermal layers in all groups. In the EGCG groups, the grafts 
    showed higher integrity in the epidermal layer and dermal matrix. The 
    present findings suggest the future clinical usefulness of EGCG for skin 
    preservation; however, the mechanism by which EGCG promotes skin 
    preservation still remains unclear.
PMID: 19775511

Snip: " increased drug deposition by 20-fold"

J Dermatol Sci. 2006 May;42(2):101-9. Epub 2006 Jan 19.

Effect of liposome encapsulation of tea catechins on their accumulation in basal
cell carcinomas.

    Fang JY, Lee WR, Shen SC, Huang YL. Pharmaceutics Laboratory, Graduate 
    Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, and
    Department of Dermatology, Taipei Medical Unversity Hospital, Taiwan.

    BACKGROUND: (-)-Epigallocatechin gallate (EGCG), the main active polyphenol 
    in green tea, is associated with antioxidant and anticancer activities. 
    OBJECTIVE: The aim of this study was to evaluate the feasibility of using 
    liposomes for intratumor distribution of EGCG and its derivative, 
    (+)-catechin. METHOD: Liposomes containing egg phosphatidylcholine, 
    cholesterol, or anionic surfactant in the presence of 15% ethanol were 
    prepared. The physicochemical characteristics including vesicle size, zeta 
    potential, drug entrapment, and drug release of liposomal formulations were 
    determined. The liposomes containing EGCG were injected into basal cell 
    carcinomas (BCCs), melanomas, and colon tumors to examine the tumor uptake 
    of the drug. Liposomes were also incubated with a given number of BCC cells,
    and the cell viability was estimated. RESULT: Almost no drug molecules were
    observed when free EGCG was administered to BCCs. EGCG encapsulated in 
    liposomes with deoxycholic acid (DA) and ethanol increased drug deposition 
    by 20-fold as compared to the free form. The larger vesicle size of this 
    formulation was suggested to be the predominant factor governing this 
    enhancement. The liposomes without ethanol showed low or negligible 
    enhancement on EGCG uptake in BCCs. Liposomes protected EGCG from 
    degradation, resulting in the induction of greater BCC death compared to 
    that by free EGCG at lower concentrations. CONCLUSION: These results suggest
    that the intratumor injection of liposomes containing EGCG with moderate 
    modification is an effective approach for increasing EGCG deposition in 
    BCCs.
PMID: 16423506


Snip: >" infiltration limit for polyphenol solution into neural tissue is 
inferred to be 500-700 microm."

J Neurosci Methods. 2005 Jun 30;145(1-2):255-66.

Optimal conditions for peripheral nerve storage in green tea polyphenol: an 
experimental study in animals.

  Matsumoto T, Kakinoki R, Ikeguchi R, Hyon SH, Nakamura T. Department of 
  Orthopedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, 
  Kyoto 606-8507, Japan.

  Our previous study demonstrated successful peripheral nerve storage for 1 
  month using polyphenol solution. We here report two studies to solve residual 
  problems in using polyphenols as a storage solution for peripheral nerves. 
  Study 1 was designed to determine the optimal concentration of the polyphenol 
  solution and the optimal immersion period for nerve storage. Rat sciatic nerve
  segments were immersed in polyphenol solution at three different 
  concentrations (2.5, 1.0, and 0.5 mg/ml) for three different periods (1, 7, 
  and 26 days). Electrophysiological and morphological studies demonstrated that
  nerve regeneration from nerve segments that had been immersed in 1mg/ml 
  polyphenol solution for 1 week and in Dulbecco's modified Eagle's medium 
  (DMEM) for the subsequent 3 weeks was superior to the regeneration in other 
  treatment groups. In study 2, the permeability of nerve tissue to polyphenol 
  solution was investigated using canine sciatic nerve segments stored in 
  1.0mg/ml polyphenol solution for 1 week and in DMEM for the subsequent 3 
  weeks. Electron microscopy revealed that the Schwann cell structure within 
  500-700 microm of the perineurium was preserved, but cells deeper than 500-700
  microm were badly damaged or had disappeared. The infiltration limit for 
  polyphenol solution into neural tissue is inferred to be 500-700 microm.
PMID: 15922041

Biotechnol Lett. 2005 May;27(9):655-60.

Protection of osteoblastic cells from freeze/thaw cycle-induced oxidative stress
by green tea polyphenol.

  Han DW, Kim HH, Lee MH, Baek HS, Lee KY, Hyon SH, Park JC. Department of 
  Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong,
  Seodaemun-gu, Seoul, 120-752, Korea.

  Green tea polyphenol (GTP) together with dimethylsulphoxide (DMSO) were added 
  to a freezing solution of osteoblastic cells (rat calvarial osteoblasts and 
  human osteosarcoma cells) exposed to repeated freeze/thaw cycles (FTC) to 
  induce oxidative stress. When cells were subjected to 3 FTCs, freezing medium 
  containing 10% (v/v) DMSO and 500 mug GTP ml(-1) significantly (p<0.05) 
  suppressed cell detachment and growth inhibition by over 63% and protected 
  cell morphology. Furthermore, the alkaline phosphatase activity of 
  osteoblastic cells was appreciably maintained after

2 and 3 FTCs in this mixture. Polyphenols may thus be of use as a cell 
cryopreservant and be advantageous in such fields as cell transplantation and 
tissue engineering.
PMID: 15977073

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32039