Potential application of plant lipid transfer proteins for drug delivery.

Ligand-binding proteins show an increasing interest as drug carriers and delivery systems [Wolf FA, Brett GM. Pharmacol Rev, 1000;52:207-36]. The wide binding properties of plant non-specific lipid transfer proteins such as LTP1 also offer many unexplored possibilities for such a task. In the present paper, by using intrinsic tyrosine LTP1 fluorescence, we survey, for the first time, the binding of wheat LTP1 with various ligands having cosmetic or pharmaceutical applications. LTP1 was found to bind skin lipids such as sphingosine, sphingomyelin, and cerebroside with an affinity of about one micromolar, low enough to allow a slow release of these molecules. Ether phospholipids and an azole derivative BD56 having antitumoral and/or antileishmania properties were also shown to bind LTP1 with similar affinity. Finally, amphotericin B, which is widely used as an antifungal drug, was shown to form a complex with LTP1, although no affinity could be determined. This binding study is a prerequisite for further work aimed at developing applications in LTP-mediated transport and controlled release of low molecular weight drugs.

[1]  I. Ahmad,et al.  Stability of association of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine with liposomes is composition dependent. , 1997, Biochimica et biophysica acta.

[2]  R. Müller,et al.  Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[3]  D. Marion,et al.  The wide binding properties of a wheat nonspecific lipid transfer protein. Solution structure of a complex with prostaglandin B2. , 2000, European journal of biochemistry.

[4]  T. Walsh,et al.  Invasive pulmonary aspergillosis in patients with neoplastic diseases. , 1990, Seminars in respiratory infections.

[5]  W. Charman,et al.  Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts. , 2000, Journal of pharmaceutical sciences.

[6]  D. Marion,et al.  Structure, Biological and Technological Functions of Lipid Transfer Proteins and Indolines, the Major Lipid Binding Proteins from Cereal Kernels , 2000 .

[7]  K. T. Holland,et al.  Interaction of Propionibacterium acnes with skin lipids in vitro. , 1993, Journal of general microbiology.

[8]  N. Fisher,et al.  Fungal infection and liposomal amphotericin B (AmBisome) therapy in liver transplantation: a 2 year review. , 1999, The Journal of antimicrobial chemotherapy.

[9]  A. Zachowski,et al.  Characterisation of acyl binding by a plant lipid-transfer protein. , 1998, European journal of biochemistry.

[10]  S. Croft,et al.  Liposomal amphotericin B in drug-resistant visceral leishmaniasis , 1991, The Lancet.

[11]  H. Kawaguchi,et al.  Functional polymer microspheres , 2000 .

[12]  D. Marion,et al.  Production in Escherichia coli and site-directed mutagenesis of a 9-kDa nonspecific lipid transfer protein from wheat. , 1999, European journal of biochemistry.

[13]  R. A. Jain,et al.  The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. , 2000, Biomaterials.

[14]  C. J. Fecko,et al.  Novel therapeutic nano-particles (lipocores): trapping poorly water soluble compounds. , 2000, International journal of pharmaceutics.

[15]  S. Croft,et al.  Antileishmanial activity of the ether phospholipid ilmofosine. , 1993, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[16]  J. Lakowicz Principles of fluorescence spectroscopy , 1983 .

[17]  U. Biswas,et al.  Amphotericin versus sodium stibogluconate in first-line treatment of Indian kala-azar , 1994, The Lancet.

[18]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[19]  M. Hawkesford,et al.  Sulphur Assimilation and Effects on Yield and Quality of Wheat , 1999 .

[20]  J. Berman Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in the last 10 years. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  Ravi Kumar M.N.V. A REVIEW OF CHITIN AND CHITOSAN APPLICATIONS , 2000 .

[22]  P. Reiss,et al.  Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS‐associated cryptococcal meningitis , 1997, AIDS.

[23]  P. Wertz,et al.  Lipids and barrier function of the skin. , 2000, Acta dermato-venereologica. Supplementum.

[24]  F. Opperdoes,et al.  Ether--lipid (alkyl-phospholipid) metabolism and the mechanism of action of ether--lipid analogues in Leishmania. , 2000, Molecular and biochemical parasitology.

[25]  Marion,et al.  Steady-state tyrosine fluorescence to study the lipid-binding properties of a wheat non-specific lipid-transfer protein (nsLTP1). , 2000, Biochimica et biophysica acta.

[26]  C. Panosian,et al.  Human antiprotozoal therapy: past, present, and future , 1995, Clinical microbiology reviews.

[27]  D. Lambert Rationale and applications of lipids as prodrug carriers. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[28]  V. Cardile,et al.  ET-18-OCH3-induced cytotoxicity and DNA damage in rat astrocytes , 2000, International Journal of Developmental Neuroscience.

[29]  G. Brett,et al.  Ligand-binding proteins: their potential for application in systems for controlled delivery and uptake of ligands. , 2000, Pharmacological reviews.

[30]  D. Marion,et al.  The crystal structure of a wheat nonspecific lipid transfer protein (ns-LTP1) complexed with two molecules of phospholipid at 2.1 A resolution. , 1999, European journal of biochemistry.

[31]  M. N. R. Kumar A review of chitin and chitosan applications , 2000 .

[32]  M Ptak,et al.  Three-dimensional structure in solution of a wheat lipid-transfer protein from multidimensional 1H-NMR data. A new folding for lipid carriers. , 1994, European journal of biochemistry.

[33]  C. Pouton,et al.  Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.