LPHNPs presentation is an illustration about the hybrid liposomes , types , methods and application , that gives a good idea about nanoparticles technology , the information has been collected from different references .

1. Hybrid Liposomes
(LPHNPS)
Dr Ahmad Adbulhusaain Yosef
Department of Pharmaceutical
2019/2020
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2. Overview of Hybrid Liposomes
( Lipid Polymers Hybrid Nano-Particle System)
 Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation to
core-shell nanostructures, conceptually derived from both liposome
and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer.
 Hybrid liposomes (HLs) are composed of vesicular and micellar molecules that can be
prepared simply by sonication of those molecules in a buffer solution without
contamination by organic solvents
Different types of lipid-polymer hybrid nanoparticles.
 1. Polymer core lipid shell.
 2. Core-lipid-polymer-lipid hybrid nanoparticle (CLPLHNs)
 3. Erythrocyte membrane-camouflaged polymeric nanoparticles.
 4. Monolithic lipid-polymer hybrid nanoparticles.
 5. Polymer caged liposomes.
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3. 3
1. Polymer core lipid shell. 2. Core-shell type lipid
polymer-lipid hybrid NPs
3. Erythrocyte membrane-camouflaged
polymeric nanoparticles.
4. Monolithic lipid-polymer hybrid nanoparticles. 5. Polymer caged liposomes

4. Topics
 Introduction
 Challenging : Stability , longer t1/2 and leakage
 HLs properties
 Types of LPHNPs
 Composition and components of LPHNPs
 Characterization of LPHNPs
 Method of preparation
 Application of LPHNPs
 Summary
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5. Introduction
Polymer Nano-particles
 Core-shell structured nanoparticles to encapsulate a wide variety
of therapeutic and diagnostic agents (theranostics) .
 Amphiphilic polymers are used in the formation of nanoparticles
with a hydrophobic core and a hydrophilic shell .
 It could be prepared from both natural polymers (e.g., chitosan)
and synthetic biodegradable and biocompatible polymers (e.g.,
poly-lactic acid and PEG ).
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6. Hybrid-Liposomes properties
 Liposomes are simple microscopic vesicles in which an aqueous volume is
entirely enclosed by a membrane composed of lipid molecule and ideal drug
delivery vehicles because of biocompatibility, analogue of biological
membranes, which can be prepared from both natural and synthetic
phospholipids , but has a defect with (t1/2 and premature release )
 HLs is an advanced theranostic Nano-medicine , it is a multifunctional
approach which combines the diagnosis and effective therapy of diseased
tissues. The influence of cholesterol (or lipid ) on the stability of the liposomes
has been intensively investigated, and revealed that lipid layer in sufficient
quantity reduces the leakage of loaded materials from liposome by increasing
their stability and decreasing their permeability (the problem with conventional
liposomes)also it could enhance the hydrophobicity of the membrane .6

7. Further characteristics of LPHNPs
 High structural integrity, stability during storage, and controlled
release capability attributed to the polymer core
 High biocompatibility and bioavailability owed to the lipid and
lipid–PEG layers
 In addition, the inner lipid layer also functions as a molecular fence
that minimizes leakage of the encapsulated content during the
LPHNPs preparation
 Furthermore, the inner lipid layer slows down the polymer
degradation rate of the LPHNPs product by limiting inward water
diffusion, hence enabling sustained release kinetics of the content
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8. Types of LPHNPs
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9. 1. Polymer core–lipid shell /
Core lipid-Polymer-Lipid System
It is composed of
 An inner aqueous core surrounded by lipid layer
 A polymer layer in between
 An outer lipid–PEG shell. and layers of the
lipid provide several advantages
1• Adjustable particle size and drug release
2• Ease of loading multiple agents
3• Better loading efficiency
4• Serum stability 9

10. 2. Polymer caged liposomes
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An improved liposome system that
can target more specifically, with
faster release kinetics and lower
general leaking, by producing a very
unstable liposome (loaded with
hyperosmotic vehicle) that is
subsequently stabilized by a cross-
linked polymer shell containing for
example cancer-associated proteases
(protease-triggered,caged
liposomes).

11. 3. Erythrocyte membrane-camouflaged
polymeric
 By coating biodegradable
polymeric nanoparticles with
natural erythrocyte membranes,
including both membrane lipids
and associated membrane
proteins for long-circulating
cargo delivery system .
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12. 4. Monolithic lipid-polymer hybrid
nanoparticles.
 Monolithic LPHNs are also known as
mixed lipid-polymer hybrid
nanoparticles. In this type
of nanoparticle lipid or lipid PEG
molecules are distributed in
a polymeric core matrix which
contains drug molecules.
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13. Composition of LPHNPs
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14. Characterization of LPHNPs
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Particle size distribution , Dynamic light scattering

15. Methods of preparation
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16. 1. Two Steps synthesis approach
 Conventional two-step method
 The polymeric core and lipid shell are prepared separately using two independent
processes; then the two components are combined by direct hydration, sonication, or
extrusion to obtain the desired lipid shell–polymer core structure
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17. Two steps synthesis approaches
 STEP 1:
 Preparation of polymeric nanoparticles by emulsification solvent evaporation
(EME), Nano-precipitation or high pressure homogenization
 STEP 2:
 Preparation of lipid vesicles in the form of a thin dried film. Lipid is first
dissolved in an organic solvent, like chloroform. Subsequently it is subjected
to rotary evaporator. The next step is the hydration of this dried lipid film by
solution of polymeric NPs . Lipid vesicles prepared by above mentioned
method will be exposed to different mixing protocols such as
Vortexing ( It is a low energy mixing process ) and Ultra sonication .
Thin dry film lipid in CHCl3===Rotary Evaporator ==== Hydration with PNs===Ultrasonication
Vortexing
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18. Managing the formulation parameters in Two-
Step Method
 Size homogeneity of the preformed lipid vesicles :
Preformed vesicles prepared by extrusion were smaller and more uniform in size
compared to vesicles formed by thin lipid film hydration
 Lipid formulation charge :
1.The monodispersity of the formed LPNs also depended on the charge of the lipid vesicles
2.Minimal LPNs aggregation (i.e., narrow size distribution and high colloidal stability) was
achieved by using only one lipid type to form vesicles
 Lipid vesicle-to-polymeric nanoparticle ratio :
1.Vesicle to nanoparticle ratio (AV/AP) significantly influenced the LPNs’ colloidal stability
2.At high AV/AP and high fractions-lipid vesicles acted as electrostatic stabilizers .
3.At low AV/AP and low fractions-Incomplete lipid coating of the nanoparticle core of
one LPN led to the exposure of its anionic surface to the cationic region of another LPN .
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19. 2. One step synthesis approach
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20. One-step method by emulsification–solvent–
evaporation (ESE)
 A single ESE method is employed when the substance to be encapsulated is soluble in a water-
immiscible solvent (i.e., oil phase)
 The oil phase, which contains the polymer and the substance to be encapsulated, is added, under
constant stirring or ultra-sonication, into an aqueous phase containing the lipid to form an oil-in-
water (o/w) emulsion.
 When the oil phase is removed by evaporation, the polymer core is formed and simultaneously
 The lipid self-assembles around the polymer– thus essentially forming the LPNs 22 ESE method
typically produces larger LPNs compared to the Nano-precipitation Single emulsification
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21. Double emulsification
 Employed when the substance to be encapsulated is insoluble in any organic
solvents, such that it cannot be dissolved together with the polymer 23 w/o
emulsion w/o/w emulsion evaporation of the oil phase, gives rise to the LPNs
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22. Formulation parameters to be controlled
Types of lipids
Lipid to Polymer Mass Ratio L/P Ratio
 Higher L/P ratios led to concentrations higher than the critical micelle concentration
resulting in the formation of liposomes in addition to the LPNs, whereas lower L/P ratios led
to LPNs aggregation due to insufficient lipid coating
 The L/P ratio was also found to indirectly influence the encapsulation efficiency, loading,
and release kinetics of the encapsulated substance through its influence on the extent of the
lipid coating of the polymer core
Lipid Coating
 It acts as a molecular barrier that keeps the encapsulated substance inside the polymer core
during the self-assembly process results in High EE(entrapment efficiency)
 Lipid coating slows down the drug release kinetics by keeping the dissolution fluid medium
away from the core
Lipid-PEG Fraction
 Increasing the lipid PEG fraction resulted in more stable LPNs( D ..leakage with I.. PEG
fra)
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23. Applications of LPHNPs
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24. Application of LPHNPs
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25. Summary
 PLN system is a highly versatile drug delivery platform due to its diverse selection and
combination of polymer and lipid materials and highly modifiable nanostructure using
these building blocks. Such properties allow PLN to efficiently load single or multiple
agents with vastly different physicochemical properties
 Superior efficacy and minimum tissue toxicity of PLN in pre-clinical studies suggest
great potential of LPHNPs for cancer treatments
 Despite the great progress made on synthesis, characterization and applications of the
hybrid nanoparticles, we call attention to a few key unmet challenges in further
developing this new nanoparticle platform as a robust drug delivery
 The simplicity of the synthesis process, especially the one-step self-assembly process,
dramatically increases the likelihood of producing the lipid-polymer hybrid
nanoparticles in a scalable and economical manner
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26. Number of LPHNPs publications indexed in the
PubMed database
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27. References
 1. Shidhaye, S.S.; Vaidya, R.; Sutar, S.; Patwardhan, A.; Kadam, V.J. Solid lipid nanoparticles and nanostructured lipid
carriers—Innovative generations of solid lipid carriers. Curr. Drug Deliv. 2008, 5, 324–331. [CrossRef] [PubMed]
 2. Lancelot, A.; Sierra, T.; Serrano, J.L. Nanostructured liquid–crystalline particles for drug delivery. Expert Opin. Drug Deliv.
2014, 11, 547–564. [CrossRef] [PubMed]
 3. Pardeike, J.; Hommoss, A.; Muller, R.H. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products.
Int. J. Pharm. 2009, 366, 170–184. [CrossRef] [PubMed]
 4. Liu, C.H.; Wu, C.T. Optimization of nanostructured lipid carriers for lutein delivery. Colloid Surf. A 2010, 353, 149–156.
[CrossRef]
 5. Zhang, W.L.; Gu, X.; Bai, H.; Yang, R.H.; Dong, C.D.; Liu, J.P. Nanostructured lipid carriers constituted from high-density
lipoprotein components for delivery of a lipophilic cardiovascular drug. Int. J. Pharm. 2010, 391, 313–321. [CrossRef]
[PubMed]
 6. Kretlow, J.D.; Klouda, L.; Mikos, A.G. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv. Drug
Deliv. Rev. 2007, 59, 263–273. [CrossRef] [PubMed]
 7. Yang, X.Z.; Dou, S.; Wang, Y.C.; Long, H.Y.; Xiong, M.H.; Mao, C.Q.; Yao, Y.D.; Wang, J. Single-step assembly of cationic
lipid–polymer hybrid nanoparticles for systemic delivery of siRNA. ACS Nano 2012, 6, 4955–4965. [CrossRef] [PubMed]
 8. Hao, T.N.; Qiao, M.X.; Li, Z.; Chen, D.W. Progress in the study of pH and temperature sensitive biodegradable block
copolymers. Acta Pharm. Sin. 2008, 43, 123–127.
 9. Beija, M.; Salvayre, R.; Lauth-de Viguerie, N.; Marty, J.D. Colloidal systems for drug delivery: From design to therapy.
Trends Biotechnol. 2012, 30, 485–496. [CrossRef] [PubMed]
 10. Peetla, C.; Stine, A.; Labhasetwar, V. Biophysical interactions with model lipid membranes: Applications in
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