Targeted drug delivery systems

1. Bilosome and Emulsomes
Presented by-
Parimal Hadge
PE/2019/311
Sub-; PE-650

2. Contents
Introduction
Advantages
Preparation of Bilosome and Emulsome
Characterization
References
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3. Biosomes and Emulsomes
Bilosomes
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Introduction
 Biosomes are consist of deoxycholic acid incorporated into membrane of neosomes.(Bile
salt commonly use as penetration enhancer and increase bioavailability..)
 Biosomes are specialized delivery vehicles which protect vaccines from being broken
down into the stomach , thereby enabling the oral delivery of vaccines as an alternative
to administrating treatment by injection.
 In 2004, Mann et.al. developed nonionic surfactant vesicles, having liposomes use
structures and stabilize then with bile salt for oral delivery of vaccine hence called
BILOSOME.
 Different from liposomes and niosomes.
 Not only prevent antigen from degradation but also enhanced mucosal penetration.
 Developed as novel lipoidal vesicular system with internal solid fat core surrounded by
phospholipid bilayer.
 This technology is designed to act as vehicle for poorly soluble drugs.
 The drug is enclosed in the emulsomes and provide prolong existence of drug in systemic
circulation.
Emulsomes

4. Bilosome and Emulsomes
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5. Advantages
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 Non invasive system offer user acceptance and compliance.
 Less toxicity envelope suitable for wide range of therapeutic agents .
 The conventional injection method suffer from high relative cost and requires trained
person to administer treatment.
 Immune response can be manipulated by controlling size and carrying vesicles.
 Allow small quantity of antigen to be effective and also increases efficacy of antigen
which are weak when injected.
 They do not requires the use of live pathogens making them safe and effective
alternative to traditional vaccines.
 Bilosomes removes cold chain requirement for preparation like vaccines.
Emulsomes
 They defend drug from harsh gastric environment of stomach before oral
administration because the drug is enclosed in the triglyceride lipid core.
 They increase the solubility and bioavailability of poorly aqueous soluble drugs.
 They provide significantly modify the pharmacokinetics of drugs.
 Emulsome based system showed excellent potential for targeting.
 They are economical alternative to current commercial lipid formulations because
they reduce the dosing frequency of drug.

6. Preparation Methods for Bilosomes
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Reverse phase evaporation
 Bile salt stabilized vesicles i.e. bilosomes are prepared by a reverse-phase evaporation
method or rotary film evaporator method or dry-film dispersing method.
 Briefly, film forming agents like soybean phosphotidylcholine, sorbitan tristearate or
1- monopalmitoyl glycerol are dissolved in organic solvents such as chloroform, ether
or acetone in round bottom flask.
 The organic solvent is then removed under reduced pressure at specific temperature
(around 40 °C) on a rotary film evaporator to form a dried thin film on the side of the
flask.
 The anhydrous film is subsequently added with small amount of buffer solution
containing specified amount of bile salt like sodium deoxycholate or sodium
glycocholate to hydrate the dry film until a homogeneous dispersion is formed.
 Finally, this crude dispersion is extruded through a high pressure homogenizer to
obtain a fine colloidal bilosomes dispersion.
 This colloidal dispersion is stored at 4 °C until use.
 Optimized colloidal dispersion of bilosomes may be obtained by tuning the
homogenization parameters, phospholipid: bile salt ratio, drug: phospholipid ratio,
water: organic solvent volume ratio, interior water phase pH, and the hydration
buffer pH, which will also affect the particle size distribution and entrapment
efficiency of bilosomes.

7. Methods
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8. Emulsomes
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Methods
Ethanol injection
method
Lipid film
formation
method ( Hand
shaking method )
Sonication method
Cast film method
High pressure
extrusion
technique
Reverse phase
evaporation

9. Lipid film formation (Handshaking method)
In this method surfactants/lipids are casted as layers of film form their organic solution
using flask rotary evaporator under reduce pressure (or by hand shaking) and then casted
films are dispersed in aqueous medium.
Upon hydration, the lipids swell and peel off from the wall of round bottom flask at
temperature slightly above the phase transition temperature of surfactants used for
specific period of time (time of hydration) with constant mild shaking.
The mechanical energy is required for the swelling of lipid and dispersion of casted lipid
film is imparted by manual by manual hand shaking or by exposing the film to a steam of
water saturated nitrogen for 15 minutes followed by swelling in the aqueous medium
without shaking.
Hand shaking method produce multi lamellar vesicles (MLV) while non shaking method
produced large unilamellar vesicles (LUVs).
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Sonication method Solid lipids
 Solid lipids, cholesterol, and phosphatidylcholine in different molar ratios were
taken in a round-bottom flask and dissolved in a minimum quantity of chloroform
containing 3 or 4 drops of methanol.
 To this solution, an accurately weighed quantity of drug was dissolved.
 The organic solvent was evaporated until complete dryness under reduced
pressure using a rotary evaporator to form a thin lipid film on walls of the round
bottom flask.

10. EVALUATION
Dynamic light scattering instrument , Laser diffraction particle size analyzer
Mean particle size is measured by Photon correlation microscopy.
Polydispersity Index
Dynamic light scattering instrument (DLS)
Zeta Potential
Dynamic light scattering instrument (DLS )
Morphology
Transmission electron microscopy (TEM)
Scanning electron microscopy (SEM)
Entrapment efficiency percent
High performance liquid chromatography (HPLC)
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The dried film was hydrated with phosphate-buffered saline pH 7.4 (10 mL) and
homogenized by ultrasonication for 15 minutes at 40% frequency to obtain emulsomes
of nanosize range.
Particle size

11. Cont.
In vitro release
Dynamic dialysis method
Separation of free drug from drug-loaded vesicles
Ultracentrifugation
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12. Some Bilosomes based vaccines preparations
• Influenza vaccine
• Titanous toxoid vaccine
• Influenza subunit
• Hepatitis B vaccine
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Some Emulsomes based vaccines preparations
Silybin Emulsomes
Case Study
Amphotericin-B Emulsomes
The antifungal agent, has been complexed with lipid to develop a less toxic
formulation of AmB.
AmB was formulated in trilaurin based nanosized lipid particles
(emulsomes).Stabilized by soyaphosphatidylcholine as new IVDD system for
macrophage targeting emulsomes prepared by cast film technique..

13. Cont.
• Formulation were optimized for AmB to lipid ratio , sonication time
to obtain particle of nanometric size range.
• Emulsomes were modified by coating them with macropahges
specific ligand.( O-palmitoyl mannan )
• Characterization was done.
• They conclude that OPM coated emulsomes could fuse with
macrophage of liver and spleen due to ligand receptor interaction .
• The praposed OPM coated emulsomes based system showed
excellent potential for passive and active intramacrophage targeting,
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14. References
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Aburahma MH. Bile salts-containing vesicles: promising pharmaceutical carriers
for oral delivery of poorly water-soluble drugs and peptide/protein-based
therapeutics or vaccines. Drug delivery. 2016 Jul 23;23(6):1847-67.
Chilkawar R, Nanjwade B, Nwaji M, Idris S, Mohamied A. Bilosomes based drug
delivery system. J. Chem. Appl. 2015;2(5).
Ahmad J, Singhal M, Amin S, Rizwanullah M, Akhter S, Amjad Kamal M, Haider
N, Midoux P, Pichon C. Bile salt stabilized vesicles (bilosomes): a novel nano-
pharmaceutical design for oral delivery of proteins and peptides. Current
pharmaceutical design. 2017 Mar 1;23(11):1575-88.
Kumar R, Seth N. Emulsomes: An emerging vesicular drug delivery system.
Journal of drug delivery and therapeutics. 2013 Nov 14;3(6):133-42.

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