Liposomal delivery of proteins and peptides

Introduction: A number of delivery issues exist for biotech molecules including peptides, proteins and gene-based medicines that now make up over 60% of the drug pipeline. The problems comprise pharmaceutical ad biopharmaceutical issues. One of the common approaches to overcome these issues is the use of a carrier and liposomes as carriers have been investigated extensively over the last decade. Areas covered: The review has been discussed in terms of formulation and preclinical development studies and in vivo studies encompassing different delivery routes including parenteral, oral, buccal, pulmonary, intranasal, ocular and transdermal involving liposomes as carriers. Important research findings have been tabulated under each side heading and an expert opinion has been summarised for each delivery route. Expert opinion: The conclusion and expert opinion – conclusion sections discuss in detail troubleshooting aspects related to the use of liposomes as carriers for delivery of biopharmaceutical moieties and scrutinises the aspects behind the absence of a protein/peptide-containing liposome in market.

[1]  Yvonne Perrie,et al.  Comparison of vesicle based antigen delivery systems for delivery of hepatitis B surface antigen. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[2]  J. Goerke,et al.  Pulmonary surfactant: functions and molecular composition. , 1998, Biochimica et biophysica acta.

[3]  K. Ito,et al.  Influence of liposomes on tryptic digestion of insulin. , 1993, Biological & pharmaceutical bulletin.

[4]  B. Wollenberg,et al.  Liposomal transfection of squamous carcinoma cells of the head and neck with IL-2 and B7 plasmids inducing an autologous immune response in vitro. , 2005, Anticancer research.

[5]  C. Ehrhardt,et al.  Liposomes for Pulmonary Drug Delivery , 2011 .

[6]  K. Skubitz,et al.  Inhalational interleukin-2 liposomes for pulmonary metastases: a phase I clinical trial , 2000, Anti-cancer drugs.

[7]  M. Kisel,et al.  Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: studies in the rat. , 2001, International journal of pharmaceutics.

[8]  I. Rubinstein,et al.  Encapsulation of vasoactive intestinal peptide into liposomes: effects on vasodilation in vivo. , 1995, Life sciences.

[9]  N. Das,et al.  Oral application of insulin encapsulated liposomes. , 1988, Biochemistry international.

[10]  Y. Barenholz,et al.  Enhancement of antitumor activity of polyethylene glycol-coated liposomal doxorubicin with soluble and liposomal interleukin 2. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[11]  J. Cherng,et al.  ENHANCEMENT OF NASAL ABSORPTION OF CALCITONIN LOADED IN LIPOSOMES , 2001, Journal of liposome research.

[12]  Yoshinori Kato,et al.  In vivo efficacy of a novel double liposome as an oral dosage form of salmon calcitonin , 2003 .

[13]  M. Naud,et al.  Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal Peptide encapsulated in liposomes. , 2007, Investigative ophthalmology & visual science.

[14]  F. Dosio,et al.  Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential , 2006, International journal of nanomedicine.

[15]  H. Jacobsson,et al.  Biodistribution of liposomal 131I-VIP in rat using gamma camera. , 2000, Nuclear Medicine and Biology.

[16]  T. Yoshikawa,et al.  A novel and simple type of liposome carrier for recombinant interleukin‐2 , 2001, The Journal of pharmacy and pharmacology.

[17]  P. Diwan,et al.  Muco-adhesive multivesicular liposomes as an effective carrier for transmucosal insulin delivery , 2007, Journal of drug targeting.

[18]  S. Balu-Iyer,et al.  Delivery of therapeutic proteins. , 2010, Journal of pharmaceutical sciences.

[19]  R. Prassl,et al.  Association of vasoactive intestinal peptide with polymer-grafted liposomes: structural aspects for pulmonary delivery. , 2007, Biochimica et biophysica acta.

[20]  R. Prassl,et al.  Liposomal vasoactive intestinal peptide for lung application: protection from proteolytic degradation. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[21]  Y. Barenholz,et al.  Delivery of Cytokines by Liposomes. II. Interleukin‐2 Encapsulated in Long‐Circulating Sterically Stabilized Liposomes: Immunomodulatory and Anti‐Tumor Activity in Mice , 1994, Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy.

[22]  J. Kawada,et al.  Effects of oral administration of positively charged insulin liposomes on alloxan diabetic rats: preliminary study. , 1979, Endocrinologia japonica.

[23]  C. Sharma,et al.  Lipoinsulin encapsulated alginate-chitosan capsules: intestinal delivery in diabetic rats , 2000, Journal of microencapsulation.

[24]  Yan Liu,et al.  Improved absorption of salmon calcitonin by ultraflexible liposomes through intranasal delivery , 2009, Peptides.

[25]  Laura Zanetti Polzi,et al.  Calcitonin forms oligomeric pore-like structures in lipid membranes. , 2006, Biophysical journal.

[26]  M. Naud,et al.  Ocular and systemic bio-distribution of rhodamine-conjugated liposomes loaded with VIP injected into the vitreous of Lewis rats , 2007, Molecular vision.

[27]  G. Storm,et al.  Liposomes: quo vadis? , 1998 .

[28]  E. Abraham,et al.  Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response. , 1992, Journal of immunology.

[29]  A. Annapragada,et al.  Glucose-sensing pulmonary delivery of human insulin to the systemic circulation of rats , 2007, International journal of nanomedicine.

[30]  Q. Ping,et al.  Transdermal delivery of insulin in mice by using lecithin vesicles as a carrier. , 2000, Drug delivery.

[31]  C. Chew,et al.  Lasp-1 is a regulated phosphoprotein within the cAMP signaling pathway in the gastric parietal cell. , 1998, American journal of physiology. Cell physiology.

[32]  Y. Oh,et al.  Pharmacodynamics of insulin in polyethylene glycol-coated liposomes. , 1999, International journal of pharmaceutics.

[33]  Ritesh Kumar,et al.  Modified Transdermal Technologies: Breaking the Barriers of Drug Permeation via the Skin , 2007 .

[34]  J. Bradshaw Phosphatydylglycerol promotes bilayer insertion of salmon calcitonin. , 1997, Biophysical journal.

[35]  L. Deftos,et al.  Liposome entrapment enhances the hypocalcemic action of parenterally administered calcitonin. , 1984, Endocrinology.

[36]  J. Parsons,et al.  Prolonged Hypoglycemic Effect in Diabetic Dogs Due to Subcutaneous Administration of Insulin in Liposomes , 1982, Diabetes.

[37]  T. Seki,et al.  Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[38]  Y. Barenholz,et al.  Delivery of cytokines by liposomes: hematopoietic and immunomodulatory activity of interleukin-2 encapsulated in conventional liposomes and in long-circulating liposomes. , 2000, Journal of immunotherapy.

[39]  S. Kawakami,et al.  Enhanced growth inhibition of metastatic lung tumors by intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes in mice , 2010, Cancer Gene Therapy.

[40]  M. Tsilimbaris,et al.  Stability of Protein-Encapsulating DRV Liposomes After Freeze-Drying: A Study with BSA and t-PA , 2006, Journal of liposome research.

[41]  T. Nagai,et al.  The relationship between the rigidity of the liposomal membrane and the absorption of insulin after nasal administration of liposomes modified with an enhancer containing insulin in rabbits. , 1999, Drug development and industrial pharmacy.

[42]  Manisha Patel,et al.  Vasodilation elicited by liposomal VIP is unimpeded by anti-VIP antibody in hamster cheek pouch. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[43]  P. Anderson,et al.  Interleukin-2 liposomes for primary immune deficiency using the aerosol route. , 2002, International immunopharmacology.

[44]  B. Dupuy,et al.  Cholate-Induced Disruption of Calcitonin-Loaded Liposomes: Formation of Trypsin-Resistant Lipid-Calcitonin-Cholate Complexes , 1995, Pharmaceutical Research.

[45]  T. Nagai,et al.  High entrapment of insulin and bovine serum albumin into neutral and positively-charged liposomes by the remote loading method. , 2000, Chemical & pharmaceutical bulletin.

[46]  T Nagai,et al.  Permeability of insulin entrapped in liposome through the nasal mucosa of rabbits. , 1992, Chemical & pharmaceutical bulletin.

[47]  J. Bystryn,et al.  Interleukin-2/liposomes potentiate immune responses to a soluble protein cancer vaccine in mice , 2006, Cancer Immunology, Immunotherapy.

[48]  I. Sayek,et al.  LIPOSOME-MEDIATED INTRAPERITONEAL INTERLEUKIN 10 GENE TRANSFER INCREASES SURVIVAL IN CECAL LITIGATION AND PUNCTURE MODEL OF SEPSIS , 2006, Shock.

[49]  I. Rubinstein,et al.  Liposomal VIP attenuates phenylephrine- and ANG II-induced vasoconstriction in vivo. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[50]  M. Naud,et al.  New formulation of vasoactive intestinal peptide using liposomes in hyaluronic acid gel for uveitis. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[51]  Jeong-Sook Park,et al.  Encapsulation enhancement and stabilization of insulin in cationic liposomes. , 2011, International journal of pharmaceutics.

[52]  P. Anderson,et al.  Nebulized Interleukin 2 Liposomes: Aerosol Characteristics and Biodistribution , 1997, The Journal of pharmacy and pharmacology.

[53]  Y. Kato,et al.  Potentiality of double liposomes containing salmon calcitonin as an oral dosage form. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[54]  Y. Kawashima,et al.  Mucoadhesive properties of carbopol or chitosan-coated liposomes and their effectiveness in the oral administration of calcitonin to rats. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[55]  T. Yoshikawa,et al.  Continuous Release of Interleukin-2 from Liposomal IL-2 (Mixture of Interleukin-2 and Liposomes) After Subcutaneous Administration to Mice , 2003, Drug development and industrial pharmacy.

[56]  A. F. Kotzé,et al.  Enhancement of nasal and intestinal calcitonin delivery by the novel Pheroid fatty acid based delivery system, and by N-trimethyl chitosan chloride. , 2010, International journal of pharmaceutics.

[57]  S. Yamashita,et al.  Application of surface-coated liposomes for oral delivery of peptide: effects of coating the liposome's surface on the GI transit of insulin. , 1999, Journal of pharmaceutical sciences.

[58]  T. Nagai,et al.  Dipalmitoylphosphatidylcholine liposomes with soybean-derived sterols and cholesterol as a carrier for the oral administration of insulin in rats. , 1996, Biological & pharmaceutical bulletin.

[59]  M. C. Popescu,et al.  Biopharmaceutics of liposomal interleukin 2, oncolipin. , 2000, Cytokine.

[60]  Q. Ping,et al.  Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice. , 2004, Acta pharmacologica Sinica.

[61]  S. Antimisiaris,et al.  Heparin incorporating liposomes as a delivery system of heparin from PET-covered metallic stents: effect on haemocompatibility. , 2006, Biomaterials.

[62]  R. J. Kelleher,et al.  IL-12 delivered intratumorally by multilamellar liposomes reactivates memory T cells in human tumor microenvironments. , 2009, Clinical immunology.

[63]  A. Duits,et al.  Immunoadjuvant activity of a liposomal IL-6 formulation. , 1993, Vaccine.

[64]  D. Hess,et al.  Nebulizers: principles and performance. , 2000, Respiratory care.

[65]  Y. Kawashima,et al.  Enteral Absorption of Insulin in Rats from Mucoadhesive Chitosan-Coated Liposomes , 1996, Pharmaceutical Research.

[66]  Y. Kawashima,et al.  Properties of liposomes coated with hydrophobically modified chitosan in oral liposomal drug delivery. , 2006, Die Pharmazie.

[67]  T Nagai,et al.  Remote loading of diclofenac, insulin and fluorescein isothiocyanate labeled insulin into liposomes by pH and acetate gradient methods. , 1999, International journal of pharmaceutics.

[68]  Ching-Hua Wang,et al.  Pulmonary delivery of insulin by liposomal carriers. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[69]  J. Kling Inhaled insulin's last gasp? , 2008, Nature Biotechnology.

[70]  V. Labhasetwar,et al.  Liposomes as a carrier for oral administration of insulin: effect of formulation factors. , 1994, Journal of microencapsulation.

[71]  W. Ahn,et al.  Topical delivery of interleukin‐13 antisense oligonucleotides with cationic elastic liposome for the treatment of atopic dermatitis , 2009, The journal of gene medicine.

[72]  Qun Wang,et al.  Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery. , 2008, Journal of drug targeting.

[73]  A. Weiner Liposomes for protein delivery: selecting manufacture and development processes. , 1994, ImmunoMethods.

[74]  X. Cao,et al.  Efficient inducation of local and systemic antitumor immune response by liposome-mediated intratumoral co-transfer of interleukin-2 gene and interleukin-6 gene. , 1999, Journal of experimental & clinical cancer research : CR.

[75]  G. Gregoriadis,et al.  The immunological co-adjuvant action of liposomal interleukin-2: the role of mode of localisation of the cytokine and antigen in the vesicles. , 1998, Journal of drug targeting.

[76]  I. Rubinstein,et al.  Encapsulation of VIP into liposomes restores vasorelaxation in hypertension in situ. , 1996, The American journal of physiology.

[77]  M. Naud,et al.  Protective effect of intravitreal injection of vasoactive intestinal peptide-loaded liposomes on experimental autoimmune uveoretinitis. , 2009, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[78]  S. Law,et al.  Characterization of calcitonin-containing liposome formulations for intranasal delivery. , 2001, Journal of microencapsulation.

[79]  T. Nagai,et al.  Double Liposomes: Hypoglycemic Effects of Liposomal Insulin on Normal Rats , 2003, Drug development and industrial pharmacy.

[80]  I. Rubinstein,et al.  Interactions of VIP with rigid phospholipid bilayers: implications for vasoreactivity , 2003, Peptides.

[81]  A. Ulrich Biophysical Aspects of Using Liposomes as Delivery Vehicles , 2002, Bioscience reports.

[82]  C. Shim,et al.  Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes containing bile salts. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[83]  T. Tadakuma,et al.  Effect of liposomal interleukin‐2 on ascites‐forming rat hepatoma , 1992, Journal of surgical oncology.

[84]  I. Rubinstein,et al.  Intratracheal and subcutaneous liposomal VIP normalizes arterial pressure in spontaneously hypertensive hamsters. , 2006, International journal of pharmaceutics.

[85]  K. Kanamura,et al.  Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis. , 2011, International journal of pharmaceutics.

[86]  I. Rubinstein,et al.  Vasoactive intestinal peptide encapsulated in liposomes: effects on systemic arterial blood pressure. , 1994, Life sciences.

[87]  P. Anderson,et al.  Aerosol delivery of interleukin 2 liposomes is nontoxic and biologically effective: canine studies. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[88]  P. Perrin,et al.  Enhancement of interleukin-2 activity by liposomes. , 1990, Vaccine.

[89]  B. Weiss-Steider,et al.  Characterization of cationic liposomes having IL-2 expressed on their external surface, and their affinity to cervical cancer cells expressing the IL-2 receptor , 2009, Journal of drug targeting.

[90]  Y. Chebloune,et al.  Therapy of ‘SHIV’ infected macaques with liposomes delivering antisense interleukin-4 DNA , 2006, AIDS.

[91]  M. Bally,et al.  Techniques for encapsulating bioactive agents into liposomes. , 1986, Chemistry and physics of lipids.

[92]  Z. Değim,et al.  The effect of various liposome formulations on insulin penetration across Caco-2 cell monolayer. , 2004, Life sciences.

[93]  S. Nakagawa,et al.  Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[94]  Kozo Takayama,et al.  Novel Mucosal Insulin Delivery Systems Based on Fusogenic Liposomes , 2005, Pharmaceutical Research.

[95]  P. Anderson,et al.  Interleukin‐2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases , 1997, Cancer.

[96]  J. Cáceres-Cortés,et al.  Cationic liposomes bearing IL-2 on their external surface induced mice leukocytes to kill human cervical cancer cells in vitro, and significantly reduced tumor burden in immunodepressed mice , 2011, Journal of drug targeting.

[97]  A. Annapragada,et al.  Triggered release of inhaled insulin from the agglomerated vesicles: pharmacodynamic studies in rats. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[98]  G. Gregoriadis,et al.  Interleukin-15 acts as an immunological co-adjuvant for liposomal antigen in vivo. , 1997, Immunology letters.

[99]  Yuquan Wei,et al.  Gene therapy for psoriasis in the K14‐VEGF transgenic mouse model by topical transdermal delivery of interleukin‐4 using ultradeformable cationic liposome , 2010, The journal of gene medicine.