Modified liposomes

Modified liposomes

1. Modified Liposomes Presented by: Vipul Sansare Bombay College of Pharmacy, Mumbai Dept. Pharmaceutics Roll No.11 26/06/2017 1

2. Liposomes Introduction : Spherical vesicles with phospholipid bilayer 26/06/2017 2

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4. Why modification?? 26/06/2017 4

5. Drug targeting using modified nanocarrier . 26/06/2017 5

6. Modification SP5-52,RGD peptide, Antimicrobial peptide PEG, Polyacrylate Mannose,galactose Anti-CD74 LL1, Anti-CD19 26/06/2017 6 Peptide Ligand Antibody Polymer

7. Modified liposomes A major limitation to the development of liposome is the problem of directing liposomes to tissues where they would not normally accumulate. Consequently, a great deal of effort has been made over the years to develop liposomes that have targeting vectors attached to the bilayer surface. 26/06/2017 7

8. To increase liposomal drug accumulation in the desired areas, the use of targeted liposomes with surface-attached ligands capable of recognition and binding to cells of interest has been suggested. 26/06/2017 8

9. PEGylation of liposomes Liposomes body treats them as foreign particles easily opsonized removed from the circulation long prior to completion of their function. Chemical modification with certain synthetic polymers . ‘steric stabilization’ polymer-mediated protection. C oating nanoparticles with PEG sterically hinders interactions of blood components with their surface and reduces the binding of plasma proteins to liposomes. 26/06/2017 9

10. This prevents interaction of liposomes with opsonins and slows down their capture by the RES . Mechanisms of preventing opsonization by PEG include 1) increased surface hydrophilicity , 2)repulsive interaction between liposome &blood components 3) impermeable polymer layer over liposome. l 26/06/2017 10

11. PEG provides : excellent solubility in aqueous solutions, high flexibility , very low toxicity, absent immunogenicity. Nom biodegradable, does not form toxic metabolites . molecular weight < 40 kDa are readily excretable via kidneys. Modification of PEG: 1)p- nitrophenylcarbonyl -PEG-PE 2) with hydrazine group (in case of antibody attachment, hydrazine reacts with the oxidized carbohydrate groups in the oligosaccharide moiety of the antibody ) 26/06/2017 11

12. Galactose modified liposomes Mucosal surfaces : respiratory, gastrointestinal and genital tract main entry site for most environmental antigens. Thus mucosal immunity play a critical role in preventing initial infection by pathogens. The mucosal immune system produces secretory IgA. A galactose -modified liposome can be specifically recognized by macrophage. Saccharification modification enhances the activity of vaccines, which subsequently increases the immunity they impart . 26/06/2017 12

13. C-type lectins are molecules on macriphages recognize carbohydrates and play a significant role in cellular recognition through carbohydrate ligands . Macrophage galactose type C-type lectins (MGLs) are type II transmembrane glycoproteins containing a single carbohydrate recognition domain. They have the capacity to bind to galactose . galactose conjugate with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) as target ligand. 26/06/2017 13

14. Preparation 26/06/2017 14 Rotary evaporator

15. Working hypothesis 26/06/2017 15

16. pH sensitive polymer- modified liposomes pH-sensitive liposomes are a promising option for antigen delivery because of their pH-responsive membrane disruption or fusion abilities, which cause the encapsulated antigen to be transferred into the cytosol . poly(acrylic acid) derivatives : used as typical pH-sensitive polymers After internalization via endocytosis induce fusion with endosomal membranes, responding to the acidic pH inside of the endosomes transfer of most of the antigen into the cytosol, as shown in the fluorescence microscopic image. leading to the induction of immune response 26/06/2017 16

17. Hydrophobic interactions :poly(carboxylic acid) main chain with the hydrophobic domain of the lipid bilayer . hydrogen bonding: the carboxyl groups of the polymer and the phosphate groups on the surface of lipid membrane. 26/06/2017 17

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19. The OVA-loaded liposomes have been added to DC2.4 cells , a murine DC line. Compared with polymer-unmodified liposomes, both the SucPG -modified and MGluPG -modified liposomes show a five-fold increase in cellular association. 26/06/2017 19

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21. Peptide modification. Integrin ᵅv ᵦ 3 and ᵅv ᵦ 5 are overexpress on tumor vasculature and selectively recognize RGD peptide. The peptide SP5-52(SVSVGMKPSPRP) recognized tumor neovasculature but not normal blood vessels. 26/06/2017 21 SVSVGMKPSPRP PEG Peptide

22. Integration of a novel antimicrobial peptide (WLBU2) into liposomes by preparing WLBU2-modified liposomes. Cationic AMP Interact with – ve charge bacterial membrane. Teichoic acid & lipopolysaccharides 26/06/2017 22

23. References Vladimir Torchilin . Antibody- modifi ed liposomes for cancer chemotherapy, Expert Opin . Drug Deliv . (2008) 5 (9): 1003-1025 Hsiao-Wen Wang a,1, Ping- Lun Jiang b,1, Shen -Fu Lin c, Hung-Jun Lin c, Keng -Liang Ouc , Win-Ping Deng c, Lin-Wen Lee d, Yi-You Huang b, Pi- Hui Liang a,⇑, Der-Zen Liu c,e . Application of galactose -modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization. Acta Biomaterialia , ( 2012):10-18. Eiji Yuba. Design of pH-sensitive polymer-modified liposomes for antigen delivery and their application in cancer immunotherapy. Polymer Journal advance online publication,(2016):1-11. Kewei Yang, a Burkhard Gitter, b Ronny R¨uger, a Gerhard D. Wieland, b Ming Chen, a Xiangli Liu, a Volker Albrecht b and Alfred Fahr. Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy. Photochemical & Photobiological Sciences. 2011, 10 , 1593–1601 26/06/2017 23

24. 26/06/2017 24 Thank You