Non-ionic surfactant based vesicles (niosomes) in drug delivery

Abstract The self assembly of non-ionic surfactants into vesicles was first reported in the seventies by researchers in the cosmetic industry. Since then a number of groups world wide have studied non-ionic surfactant vesicles (niosomes) with a view to evaluating their potential as drug carriers. This article presents a summary of the achievements in the field to date. Niosomes may be formed form a diverse array of amphiphiles bearing sugar, polyoxyethylene, polyglycerol, crown ether and amino acid hydrophilic head groups and these amphiphiles typically possess one to two hydrophobic alkyl, perfluoroalkyl or steroidal groups. The self assembly of surfactants into niosomes is governed not only by the nature of the surfactant but by the presence of membrane additives, the nature of the drug encapsulated and the actual method of preparation. Methods of niosome preparation and the number of different morphologies that have been identified are detailed. The influence of formulation factors on niosome stability is also examined as are methods to optimise drug loading. In vivo these systems have been evaluated as immunological adjuvants, anti-cancer/anti-infective drug targeting agents and carriers of anti-inflammatory drugs. Niosomes have also been used in diagnostic imaging. Efforts to achieve transdermal and ophthalmic drug delivery with some formulations are also discussed.

[1]  J. Cummings,et al.  Adriamycin-loaded niosomes: drug entrapment, stability and release. , 1987, Journal of microencapsulation.

[2]  N. Weiner,et al.  The effect of dosing volume on the disposition of cyclosporin A in hairless mouse skin after topical application of a non-ionic liposomal formulation: an in vitro diffusion study , 1994 .

[3]  A. Schätzlein,et al.  TRANSDERMAL DRUG CARRIERS - BASIC PROPERTIES, OPTIMIZATION AND TRANSFER EFFICIENCY IN THE CASE OF EPICUTANEOUSLY APPLIED PEPTIDES , 1995 .

[4]  F. Szoka,et al.  Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[5]  I. Uchegbu Some aspects of the niosomal delivery of doxorubicin. , 1994 .

[6]  S. Lesieur,et al.  Generation of non-ionic monoalkyl amphiphile-cholesterol vesicles : evidence of membrane impermeability to octyl glucoside , 1996 .

[7]  C. Roberts,et al.  Antibody responses to Toxoplasma gondii antigen in human peripheral blood lymphocyte‐reconstituted severe‐combined immunodeficient mice reproduce the immunological status of the lymphocyte donor , 1995, European journal of immunology.

[8]  G. H. Coombs,et al.  Non‐ionic surfactant vesicles, niosomes, as a delivery system for the anti‐leishmanial drug, sodium stibogluconate , 1986, The Journal of pharmacy and pharmacology.

[9]  G. Cevc Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. , 1996, Critical reviews in therapeutic drug carrier systems.

[10]  A. Florence,et al.  The preparation and properties of niosomes—non‐ionic surfactant vesicles , 1985, The Journal of pharmacy and pharmacology.

[11]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1941 .

[12]  J. Double,et al.  The activity of doxorubicin niosomes against an ovarian cancer cell line and three in vivo mouse tumour models. , 1996, Journal of drug targeting.

[13]  M. Carafa,et al.  Vesicles from polysorbate 20 and cholesterol. A simple preparation and a characterization , 1996 .

[14]  J. O'grady,et al.  The distribution of free and non-ionic vesicular sodium stibogluconate in the dog. , 1993, Journal of drug targeting.

[15]  A. Baillie,et al.  The therapeutic effect of sodium stibogluconate in BALB/c mice infected with Leishmania donovani is organ‐dependent , 1988, The Journal of pharmacy and pharmacology.

[16]  Alexander T. Florence,et al.  Vesicle (niosome)-in-water-in-oil (v/w/o) emulsions: an in vitro study , 1994 .

[17]  A. Polidori,et al.  Synthesis of double-chain glycolipids derived from aspartic acid : Preliminary investigation of their colloidal behavior , 1994 .

[18]  N. Udupa,et al.  Formulation and Evaluation of Oral and Transdermal Preparations of Flurbiprofen and Piroxicam Incorporated with Different Carriers , 1993 .

[19]  D. Kerr,et al.  Antitumour activity and pharmacokinetics of niosome encapsulated adriamycin in monolayer, spheroid and xenograft. , 1988, British Journal of Cancer.

[20]  I. Uchegbu,et al.  The evaluation of crown ether based niosomes as cation containing and cation sensitive drug delivery systems , 1997 .

[21]  M. Marchand-Arvier,et al.  [Hemoglobin niosomes. I. Preparation, functional and physico-chemical properties, and stability]. , 1989, Pharmaceutica Acta Helvetiae.

[22]  J. Moreau,et al.  Action of octylglucoside on non-ionic monoalkyl amphiphile-cholesterol vesicles: study of the solubilization mechanism , 1990 .

[23]  J. Kreuter,et al.  Colloidal Drug Delivery Systems , 1994 .

[24]  J. Bouwstra,et al.  LARGE DISK-SHAPED STRUCTURES (DISCOMES) IN NONIONIC SURFACTANT VESICLE TO MICELLE TRANSITIONS , 1992 .

[25]  A. Baillie,et al.  Visceral leishmaniasis in the BALB/c mouse: a comparison of the in vivo activity of five non-ionic surfactant vesicle preparations of sodium stibogluconate. , 1995, Journal of drug targeting.

[26]  M. Graetzel,et al.  Light-induced charge injection in functional crown ether vesicles , 1980 .

[27]  H. Junginger,et al.  Interactions of non-ionic surfactant vesicles with cultured keratinocytes and human skin in vitro: a survey of toxicological aspects and ultrastructural changes in stratum corneum , 1991 .

[28]  N. Udupa,et al.  Niosome encapsulated of vincristine sulfate: improved anticancer activity with reduced toxicity in mice. , 1994, Journal of drug targeting.

[29]  G. H. Coombs,et al.  Vesicular Systems (Niosomes and Liposomes) for Delivery of Sodium Stibogluconate in Experimental Murine Visceral Leishmaniasis , 1988, The Journal of pharmacy and pharmacology.

[30]  H. Junginger,et al.  Safety Aspects of Non‐ionic Surfactant Vesicles: A Toxicity Study Related to the Physicochemical Characteristics of Non‐ionic Surfactants , 1992, The Journal of pharmacy and pharmacology.

[31]  K. Ulbrich,et al.  Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers. 3. Evaluation of adriamycin conjugates against mouse leukaemia L1210 in vivo , 1989 .

[32]  B. Pucci,et al.  Vesicles and other supramolecular systems from biocompatible synthetic glycolipids with hydrocarbon and/or fluorocarbon chains. , 1994, Chemistry and physics of lipids.

[33]  C. Jain,et al.  Preparation and characterization of niosomes containing rifampicin for lung targeting. , 1995, Journal of microencapsulation.

[34]  A. Schätzlein,et al.  Polyhedral Non‐ionic Surfactant Vesicles , 1997, The Journal of pharmacy and pharmacology.

[35]  Minako Tanaka,et al.  Properties of the aqueous vesicle dispersion formed with poly(oxyethylene) hydrogenated castor oil , 1990 .

[36]  G. Cevc Electrostatic characterization of liposomes , 1993 .

[37]  A. Florence,et al.  A non-ionic surfactant vesicle-in-water-in-oil (v/w/o) system: potential uses in drug and vaccine delivery. , 1995, Journal of drug targeting.

[38]  R. Duncan,et al.  Polymer Conjugates , 1994 .

[39]  R. Duncan,et al.  Niosomes containing N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin (PK1) : effect of method of preparation and choice of surfactant on niosome characteristics and a preliminary study of body distribution , 1997 .

[40]  T. Kunitake,et al.  Synthetic bilayer membranes prepared from dialkyl amphiphiles with nonionic and zwitterionic head groups , 1981 .

[41]  R. Handjani-Vila,et al.  Dispersions of lamellar phases of non‐ionic lipids in cosmetic products , 1979, International journal of cosmetic science.

[42]  Robert C. Hider,et al.  Liposome formation from synthetic polyhydroxyl lipids. , 1991, Biochimica et biophysica acta.

[43]  S. Lesieur,et al.  Kinetic aspects of the solubilization of non-ionic monoalkyl amphiphile-cholesterol vesicles by octylglucoside , 1992 .

[44]  G Blume,et al.  Liposomes for the sustained drug release in vivo. , 1990, Biochimica et biophysica acta.

[45]  M. Carafa,et al.  Preparation and properties of new unilamellar non-ionic/ionic surfactant vesicles , 1998 .

[46]  S. Yamada,et al.  Application of synthetic alkyl glycoside vesicles as drug carriers. I. Preparation and physical properties. , 1985, Chemical & pharmaceutical bulletin.

[47]  J. Brewer,et al.  Lipid vesicle‐entrapped influenza A antigen modulates the influenza A‐specific human antibody response in immune reconstituted SCID‐human mice , 1996, European journal of immunology.

[48]  M. Carafa,et al.  Non-ionic surfactant vesicles as ophthalmic carriers for cyclopentolate. A preliminary evaluation , 1996 .

[49]  D. Lasič On the thermodynamic stability of liposomes , 1990 .

[50]  G. Gokel,et al.  Aggregation of steroidal lariat ethers: the first example of nonionic liposomes (niosomes) formed from neutral crown ether compounds , 1988 .

[51]  I. Uchegbu,et al.  Non-ionic surfactant vesicles (niosomes): Physical and pharmaceutical chemistry , 1995 .

[52]  H. Junginger,et al.  Niosomes for oral delivery of peptide drugs , 1992 .

[53]  J. Bouwstra,et al.  Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery , 1994 .

[54]  C. Cable An examination of the effect of surface modifications on the physicochemical and biological properties of non-ionic surfactant vesicles , 1990 .

[55]  I. Uchegbu The biodistribution of novel 200-nm palmitoyl muramic acid vesicles , 1998 .

[56]  R. New,et al.  Liposomes : a practical approach , 1990 .

[57]  Vyas Sp,et al.  Lymphatic delivery of niosome encapsulated methotrexate. , 1995 .

[58]  L. Mayer,et al.  Vesicles of variable sizes produced by a rapid extrusion procedure. , 1986, Biochimica et biophysica acta.

[59]  B. Pucci,et al.  Alkyl and perfluoroalkyl glycolipid-based supramolecular assemblies , 1994 .

[60]  H. Junginger,et al.  Liposomes and niosomes : interactions with human skin , 1991 .

[61]  A. Florence,et al.  Non-ionic surfactant based organogels incorporating niosomes , 1996 .

[62]  A. Bangham,et al.  Diffusion of univalent ions across the lamellae of swollen phospholipids. , 1965, Journal of molecular biology.

[63]  N. Udupa,et al.  Formulation and Evaluation of Methotrexate Niosomes , 1993 .

[64]  A. Schätzlein,et al.  The skin: a pathway for systemic treatment with patches and lipid-based agent carriers , 1996 .

[65]  H. Junginger,et al.  Diffusion of estradiol from non-ionic surfactant vesicles through human stratum corneum in vitro , 1996 .

[66]  R. Duncan,et al.  Pharmaceutical and biological characterisation of a doxorubicin-polymer conjugate (PK1) entrapped in sorbitan monostearate Span 60 niosomes , 1997 .

[67]  A. Florence,et al.  Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20, 40, 60 and 80) and a sorbitan triester (Span 85) , 1994 .

[68]  I. Uchegbu,et al.  The Effect of Monomers and of Micellar and Vesicular Forms of Non‐ionic Surfactants (Solulan C24 and Solulan 16) on Caco‐2 Cell Monolayers , 1997, The Journal of pharmacy and pharmacology.

[69]  A. Florence,et al.  The effect of non‐ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice , 1985, The Journal of pharmacy and pharmacology.

[70]  J. Brewer,et al.  The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB/c humoral response to bovine serum albumin. , 1992, Immunology.

[71]  H. Kiwada,et al.  Tissue distribution and pharmacokinetic evaluation of the targeting efficiency of synthetic alkyl glycoside vesicles. , 1985, Chemical & pharmaceutical bulletin.

[72]  J. Cummings,et al.  The Distribution of Doxorubicin in Mice Following Administration in Niosomes , 1988, The Journal of pharmacy and pharmacology.

[73]  Gregory Gregoriadis,et al.  Dehydration-Rehydration Vesicles: A Simple Method for High Yield Drug Entrapment in Liposomes , 1984, Bio/Technology.

[74]  D. Crommelin,et al.  A novel technique for the one-step preparation of liposomes and nonionic surfactant vesicles without the use of organic solvents. Liposome formation in a continuous gas stream: the 'bubble' method. , 1994, Journal of pharmaceutical sciences.

[75]  D. Hoekstra,et al.  Vesicle-forming synthetic amphiphiles. , 1995, Biochimica et biophysica acta.

[76]  S. Lesieur,et al.  Solubilization of Nonionic Monoalkyl Amphiphile−Cholesterol Vesicles by Octyl Glucoside: Cryo-Transmission Electron Microscopy of the Intermediate Structures , 1996 .

[77]  G. Trapani,et al.  Determination of hydrophile-lipophile balance of some polyethoxylated non-ionic surfactants by reversed-phase thin layer chromatography , 1995 .

[78]  J. Double,et al.  Drug distribution and a pulmonary adverse effect of intraperitoneally administered doxorubicin niosomes in the mouse , 1994, Biopharmaceutics & drug disposition.

[79]  Phase transitions in aqueous dispersions of the hexadecyl diglycerol ether (C(16)G(2)) non-ionic surfactant, cholesterol and cholesteryl poly-24-oxyethylene ether: Vesicles, tubules, discomes and micelles , 1996 .

[80]  Y. Barenholz,et al.  Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. , 1993, Biochimica et biophysica acta.

[81]  N. Van Rooijen,et al.  Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. , 1994, Biochimica et biophysica acta.

[82]  N. Udupa,et al.  Effect of macrophage activation on plasma disposition of niosomal 3H-methotrexate in sarcoma-180 bearing mice. , 1993, Journal of drug targeting.