Biology of Microorganisms Thomas D. Brock

Introduction, D.D. Lasic and F.J. Martin Foreword, A.D. Bangham Stealth(R) Liposomes: From Steric Stabilization to Targeting, D. Papahadjopoulos Fate of Liposomes In Vivo and Its Control: An Historical Perspective, G. Gregoriadis Effect of Surface Modification with Glycolipids and Polysaccharides on In Vivo Fate of Liposomes, P.C. Ghosh and B.K. Bachhawat Stabilization of Colloidal Dispersions by Grafted Polymers, O. Borisov, P. Auroy, and L. Auvray Physical Properties of Polymer-Grafted Bilayers, K. Hristova and D. Needham Molecular Mechanism of Liposome and Immunoliposome Steric Protection with Poly (Ethylene Glycol): Theoretical and Experimental Proofs of the Role of Polymer Chain Flexibility, V.P. Torchilin, M.I. Papisov, A.A. Bogdanov, V.S. Trubetskoy, and V.G. Omelyanenko Measurement of the Range and Magnitude of the Repulsive Pressure between PEG-Coated Liposomes, T.J. McIntosh, A.K. Kenworthy, and D. Needham Modulation and Modeling of Interaction Forces between Lipid Bilayers Exposing Terminally Grafted Polymer Chains, T.L. Kuhl, D.E. Leckband, D.D. Lasic, and J.N. Israelachvili Polyetheylene Glycol-Lipid Conjugates, S. Zalipsky Biological Properties of Sterically Stabilized Liposomes, M.C. Woodle, M.S. Newman, and P.K. Working Mechanism of Stealth(R) Liposomes Accumulation in Some Pathological Tissues, S.K. Huang, F.J. Martin, D.S. Friend, and D. Papahadjopoulos Extravasation of Stealth(R) Liposomes into Tumors: Direct Measurement of Accumulation and Vascular Permeability Using a Skin-Flap Window Chamber, M. Dewhirst and D. Needham Pharmacokinetics and Antitumor Activity of Anthracyclines Precipitated in Sterically Stabilized (Stealth(R)) Liposomes, D.D. Lasic Tissue Uptake and Therapeutic Effects of Stealth(R) Doxorubicin, J. Vaage and E. Barbera Therapeutic Application of Vincristine in Conventional and Sterically Stabilized Liposomes, P.S. Uster Stealth(R) Liposomes as a Drug Sustained Release System for 1-b-D-Arabinosylfuranosylcytosine (Cytosine Arabinoside), T.M. Allen Stealth(R) Liposomes as Carriers of Antibiotics in Infectious Diseases, I. Bakker-Woudenberg, G. Storm, and M.C. Woodle Sterically Stabilized Liposome-Encapsulated Hemoglobin, S. Zheng, Y. Zheng, and R. Beissinger PEG-Modified Liposomes for Gamma-II and Magnetic Resonance Imaging, V.P. Torchilin, J. Narula, B.A. Khaw, and V.S. Trubetskoy Antibody-Targeted Stealth(R) Liposomes, T.M. Allen, C.B. Hansen, and S. Zalipsky Doxorubicin Encapsulated in Polyethylene-Glycol Coated Liposomes: Initial Clinical-Pharmacokinetic Studies in Solid Tumors, A. Gabizon, A. Huang, F. Martin, and Y. Barenholz Pharmacokinetics and Tumor Localization of DOX-SL (Stealth(R) Liposomal Doxorubicin) by Comparison with Adriamycin in Patients with AIDS and Kaposi Sarcoma, D. Northfelt, L. Kaplan, J. Russell, and P. Volberding Efficacy of DOX-SL (Stealth(R) Liposomal Doxorubicin) in the Treatment of Advanced AIDS-Related Kaposi Sarcoma, J.R. Bogner and F.D. Goebel

Stealth「上○R上」 liposomes

Parasitism, infection and immunity the parasites viruses bacteria fungi, protozoa, worms external defences and how parasites escape them entry and exit disease due to the presence of the parasite cytopathic infections exotoxins tutorial 1 the immune system recognition molecules disposal mechanisms communication molecules cytokines natural immunity how parasites ecape natural immunity disease due to natural immunity endotoxins and TNF tutorial 2 adpative immunity the lymphocyte B cells and antibody T cells and the MHC the antibody response cell-mediated responses how parasites escape adaptive immunity tutorial 3 disease due to adaptive immunity immunopathology and hypersensitivity autoimmunity immunodeficiency primary secondary AIDS control of infectious disease vaccination chemotherapy summing up the host-parasite battle.

Infection and Immunity

Background: The present study aims to design formulation of liposomes that are well-preserved during freeze-drying. The combination of Hydroxy Propyl Methyl Cellulose (HPMC) as dispersion matrix and lyoprotectants; maltodextrin or mannitol, was employed to prevent aggregation and/or recrystallization. The obtained dry products were investigated in terms of their physical characteristics. Methods: Liposomes were prepared using thin film method and hydrated with the lyoprotectant solution. The formed liposomes were mixed with HPMC gel and freeze-dried. The obtained solid products were characterized using Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and Scanning Electron Microscopy (SEM). Results: The DSC thermograms of formulations with maltodextrin were relatively homogenous, yet exhibiting meta-stable properties. In contrast, the formulations using mannitol showed phase separation. These results were confirmed by XRD data, in which formulations with maltodextrin showed no intensive peaks, indicating amorphous solid while the formulations with mannitol exhibited more intensive peaks, indicating the presence of crystalline solids. The SEM images of both maltodextrin and mannitol-containing formulations showed porous matrix with spherical liposomes trapped in the matrices. The SEM images also correspond to the DSC and XRD data, where crystalline solid existed in the mannitol-containing formula. Conclusion: The developed liposomes formulation using combination of HPMC matrix and maltodextrin showed potential in preserving liposomes structure, contrary to those of using mannitol.

https://journals.tbzmed.ac.ir/PHARM/Manuscript/PHARM-23-285.pdf

Physical Characteristics of Liposomal Formulation Dispersed in HPMC Matrix and Freeze-Dried Using Maltodextrin and Mannitol as Lyoprotectant

Disaccharides, such as sucrose, have been reported to protect phospholipid membranes during drying,
while HPMC is used as gel matrix to inhibit recrystallization. We have investigated the solid state
characterization of dried liposome formulation (air-dried and freeze-dried) which was preserved in the
presence of sucrose and dispersed in HPMC matrix. The dried liposomal featured cationic dimethyl dioctadecyl ammonium (DDA) was produced to overcome detrimental phase
separation in phospholipid membranes during manufacturing
process. The effect of sucrose and HPMC on lipid phase behavior during dehydration were characterized including their thermodynamics by DSC, crystallinity by XRD,
and liposome structure by SEM. Data revealed that formula contain 5% sucrose and 7.5% HPMC showed a miscible mixture and relatively less crystalline-forming properties that potentially construct a stable dried liposome. The results may aid in the development of dried–DDA liposomal formulation by using combination of sucrose and HPMC.

/pdf/solid-state-characterization-of-dried-liposomes-in-the-1l3qxafdy5.pdf

Solid State Characterization of Dried Liposomes in The Presence of Sucrose and HPMC as Dispersing Matrix

Liposome systems are well reported for their activity as vaccine adjuvants; however novel lipid-based microbubbles have also been reported to enhance the targeting of antigens into dendritic cells (DCs) in cancer immunotherapy (Suzuki et al 2009). This research initially focused on the formulation of gas-filled lipid coated microbubbles and their potential activation of macrophages using in vitro models. Further studies in the thesis concentrated on aqueous-filled liposomes as vaccine delivery systems. Initial work involved formulating and characterising four different methods of producing lipid-coated microbubbles (sometimes referred to as gas-filled liposomes), by homogenisation, sonication, a gas-releasing chemical reaction and agitation/pressurisation in terms of stability and physico-chemical characteristics. Two of the preparations were tested as pressure probes in MRI studies. The first preparation composed of a standard phospholipid (DSPC) filled with air or nitrogen (N2), whilst in the second method the microbubbles were composed of a fluorinated phospholipid (F-GPC) filled with a fluorocarbon saturated gas. The studies showed that whilst maintaining high sensitivity, a novel contrast agent which allows stable MRI measurements of fluid pressure over time, could be produced using lipid-coated microbubbles. The F-GPC microbubbles were found to withstand pressures up to 2.6 bar with minimal damage as opposed to the DSPC microbubbles, which were damaged at above 1.3 bar. However, it was also found that DSPC-filled with N2 microbubbles were also extremely robust to pressure and their performance was similar to that of F-GPC based microbubbles. Following on from the MRI studies, the DSPC-air and N2 filled lipid-based microbubbles were assessed for their potential activation of macrophages using in vitro models and compared to equivalent aqueous-filled liposomes. The microbubble formulations did not stimulate macrophage uptake, so studies thereafter focused on aqueous-filled liposomes. Further studies concentrated on formulating and characterising, both physico-chemically and immunologically, cationic liposomes based on the potent adjuvant dimethyldioctadecylammonium (DDA) and immunomodulatory trehalose dibehenate (TDB) with the addition of polyethylene glycol (PEG). One of the proposed hypotheses for the mechanism behind the immunostimulatory effect obtained with DDA:TDB is the ‘depot effect’ in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. The depot effect has been suggested to be primarily due to their cationic nature. Results reported within this thesis demonstrate that higher levels of PEG i.e. 25 % were able to significantly inhibit the formation of a liposome depot at the injection site and also severely limit the retention of antigen at the site. This therefore resulted in a faster drainage of the liposomes from the site of injection. The versatility of cationic liposomes based on DDA:TDB in combination with different immunostimulatory ligands including, polyinosinic-polycytidylic acid (poly (I:C), TLR 3 ligand), and CpG (TLR 9 ligand) either entrapped within the vesicles or adsorbed onto the liposome surface was investigated for immunogenic capacity as vaccine adjuvants. Small unilamellar (SUV) DDA:TDB vesicles (20-100 nm native size) with protein antigen adsorbed to the vesicle surface were the most potent in inducing both T cell (7-fold increase) and antibody (up to 2 log increase) antigen specific responses. The addition of TLR agonists poly(I:C) and CpG to SUV liposomes had small or no effect on their adjuvanticity. Finally, threitol ceramide (ThrCer), a new mmunostimulatory agent, was incorporated into the bilayers of liposomes composed of DDA or DSPC to investigate the uptake of ThrCer, by dendritic cells (DCs), and presentation on CD1d molecules to invariant natural killer T cells. These systems were prepared both as multilamellar vesicles (MLV) and Small unilamellar (SUV). It was demonstrated that the IFN-g secretion was higher for DDA SUV liposome formulation (p<0.05), suggesting that ThrCer encapsulation in this liposome formulation resulted in a higher uptake by DCs.

Liposomes:Formulation and characterisation as contrast agents and as vaccine delivery systems

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Liposomes:Formulation and characterisation as contrast agents and as vaccine delivery systems