Phospholipid vesicles encapsulated bacteriophage: A novel approach to enhance phage biodistribution.

Phage therapy has been at the centre of attraction for combating multi-drug resistant strains. However, less stability and rapid clearance of phage by mononuclear phagocytic system (MPS) restricts its use in humans. In the present study, aim was to develop a liposomal delivery system for bacteriophage that can assure efficient phage delivery and retention at the site of infection. Different ratios of cholesterol, lipids and surfactant along with different charge inducers were employed to prepare liposomes. Phage was then entrapped in the liposomes and characterized on the basis of morphology, size, entrapment efficiency and stability. Further, in vivo biodistribution of free phage and liposome entrapped phage was compared in different organs of mice. A cationic liposomal formulation showed maximum encapsulation efficiency of 92%. Transmission electron microscopy (TEM) confirmed the entrapment of phages in liposomes. Liposome preparation was found to be most stable at 4°C during storage. Liposome entrapped bacteriophage was retained for longer duration in different organs i.e. upto day 4 in blood, day 6 in liver, lungs and kidney, 14days in spleen of mice as compared to free phage that became undetectable by 36th h in blood as well as lungs and by 48th h in all other organs.

[1]  R. Pelton,et al.  Biocontrol of Listeria monocytogenes and Escherichia coli O157:H7 in Meat by Using Phages Immobilized on Modified Cellulose Membranes , 2011, Applied and Environmental Microbiology.

[2]  Wen-Yih Chen,et al.  Microcalorimetric investigation of the interaction of polysorbate surfactants with unilamellar phosphatidylcholines liposomes , 2003 .

[3]  S Singh,et al.  Study of azathioprine encapsulation into liposomes. , 1998, Journal of microencapsulation.

[4]  M. Mathur,et al.  Bacteriophage therapy: an alternative to conventional antibiotics. , 2003, The Journal of the Association of Physicians of India.

[5]  J. Soothill.  Treatment of experimental infections of mice with bacteriophages. , 1992, Journal of medical microbiology.

[6]  M. Loessner,et al.  Bacteriophage P100 for control of Listeria monocytogenes in foods: genome sequence, bioinformatic analyses, oral toxicity study, and application. , 2005, Regulatory toxicology and pharmacology : RTP.

[7]  G. Hanlon,et al.  Bacteriophages: an appraisal of their role in the treatment of bacterial infections. , 2007, International journal of antimicrobial agents.

[8]  A. Huc,et al.  Stabilization of liposomes with collagen , 1991 .

[9]  Gajanand Sharma,et al.  Topical Delivery of Aceclofenac: Challenges and Promises of Novel Drug Delivery Systems , 2014, BioMed research international.

[10]  Raquel Manzano,et al.  Amyotrophic Lateral Sclerosis: A Focus on Disease Progression , 2014, BioMed research international.

[11]  Ijeoma F. Uchegbu,et al.  Non-ionic surfactant based vesicles (niosomes) in drug delivery , 1998 .

[12]  T. Nakae,et al.  Cytolytic activity of liposomes containing stearylamine. , 1986, Biochimica et biophysica acta.

[13]  K. Thiel,et al.  China approves first gene therapy , 2004, Nature Biotechnology.

[14]  L. Thoma,et al.  A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies. , 2006, PDA journal of pharmaceutical science and technology.

[15]  J. Lagacé,et al.  In vitro kinetics of drug release and pulmonary retention of microencapsulated antibiotic in liposomal formulations in relation to the lipid composition. , 1997, Journal of microencapsulation.

[16]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[17]  S. Chhibber,et al.  Characterization of a T7-Like Lytic Bacteriophage of Klebsiella pneumoniae B5055: A Potential Therapeutic Agent , 2009, Current Microbiology.

[18]  Sagar R. Mudshinge,et al.  Nanoparticles: Emerging carriers for drug delivery. , 2011, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[19]  G. Poste,et al.  Lipid vesicles as carriers for introducing materials into cultured cells: influence of vesicle lipid composition on mechanism(s) of vesicle incorporation into cells. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Samad,et al.  Development and Evaluation of Inhalational Liposomal System of Budesonide for Better Management of Asthma , 2010, Indian journal of pharmaceutical sciences.