Modified liposomes can be prepared with ligands, polymers, or peptides attached to increase drug targeting, circulation longevity, and stability. This includes PEGylation to prevent opsonization, galactose modification to target macrophages, and pH-sensitive polymers or peptides like RGD to modify cell interactions and targeting. Peptide and polymer modifications can enhance liposome association with cells and facilitate endosomal escape of encapsulated antigens or drugs.

1. Modified Liposomes
Presented by:
Vipul Sansare
Bombay College of Pharmacy, Mumbai
Dept. Pharmaceutics
Roll No.11
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2. Liposomes Introduction:
Spherical vesicles with phospholipid bilayer
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4. Why modification??
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Drug targeting
Circulation longevity
Stability

5. Drug targeting using modified
nanocarrier.
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6. Modification
SP5-52,RGD peptide,
Antimicrobial peptide
PEG, Polyacrylate
Mannose,galactose
Anti-CD74 LL1, Anti-CD19
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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.
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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.
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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.
• Coating nanoparticles with PEG sterically hinders interactions of
blood components with their surface and reduces the binding of
plasma proteins to liposomes.
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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
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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)
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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 .
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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.
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14. Preparation
95% Phosphatidyl
choline+cholesterol+
galactosyl lipid
(4:0.5:0.5)
(20mM)
Thin film
Hydrated with 10ml OVA
solution
(1mg/ml)
Sonication:
Bath sonicator
(40kHz)
30 min.
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Rotary evaporator

15. Working hypothesis
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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
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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.
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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.
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21. Peptide modification.
• Integrin ᵅvᵦ3 and ᵅvᵦ5 are overexpress on
tumor vasculature and selectively recognize
RGD peptide.
• The peptide SP5-52(SVSVGMKPSPRP)
recognized tumor neovasculature but not
normal blood vessels.
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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
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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,aVolker Albrechtb and Alfred Fahr. Antimicrobial
peptide-modified liposomes for bacteria targeted delivery of
• temoporfin in photodynamic antimicrobial chemotherapy.
Photochemical &
• Photobiological Sciences. 2011, 10, 1593–1601
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