polymeric micelles as smart / intelligent drug delivery

1. PRESENTED BY
MR. KIRAN N. PATANGE
M.PHARM II SEMISTER
DEPT. OF PCEUTICAL SCIENCES
RTMNU,NAGPUR

2. POINTS TO BE COVERED……….
 INTRODUCTION
 MECHANISM OF MICELLIZATION
 FACTORS AFFECTING THE PROCESS OF
MICELLES FORMATION
 WHY POLYMER MICELLSES ARE ATTRACTIVE
 TYPES OF POLYMERIC MICELLES
 TYPES OF POLYMER USED
 METHODS OF PREPARATION
 CHARACTERIATION OF POLYMERIC
MICELLES
 APPLICATIONS

3. INTRODUCTION
MICELLES:
 It is nothing but supramolecular structure i.e.
generated from self assemblage of amphiphilic
molecule
 Lie in colloidal range
 Made up of 50 to 200 monomer
AGGRGATION NO:
 It is an avg. no. of monomer which form micelles at
given time
CMC:
 The conc.of monomer at which micelles form

4. Polymeric micelles
 This are self assembled colloidal particle with
hydrophobic core and hydrophilic cell
 It is desired that is composed of
-biocompatible material(copolymer)
-has the versatility to encapsule a wide range of
therapeutic drug
-stable to dilution within blood stream

5. Machanisnm of micellization
Amphiphilic molecule + solvent
Self association of amphiphilic molecules
Polymeric micelles

6.  Self association of monomer duo to decrease in free
energy of system .
 This is due to removal of hydrophobic fragments from
aqueous surrounding with the formation of micelle
with hydrophilic fragment exposed into water .

7. Factors affecting process of
micelles formation
 Molecular wt. of monomer
 Aggregation no.
 Proportion of hydrophobic and hydrophilic chain
length
 Preparation process
 CMC

8. WHY POLYMERIC MICELLES
ARE ATRRACTIVE
Polymeric micelles have gathered attention in drug &
protein delivery due to :
 Biocompatibility
 Solubilization of hydrophobic moeities in micellar core
 More stable toward dilution & hence exhibit minimal
cytotoxicity
 Enhanced blood circulation time suitable for i.v.
administration drug delivery system
 Smart or intelligent drug carriers

9. Types of polymeric micelles
Based on intermolecular forces governing the
segregation of the core segment from aqueous
environment.
 Conventional
 Poly-ion complex micelles
 Non-covalently connected polymeric micelles

10. Conventional
 Resulting from hydrophilic interaction
e.g. Poly(ethylene oxide)-b-poly(propylene oxide)-b-
poly(ethylene oxide)
Polyion complex micelles
 Resulting from electrostatic interaction between
oppositely charged moieties such as [polyelectrolyte.
solution oppositely charged polymer polyion complex micelles

11. Features of polyion complex polymeric micelles:
 Easy self association in aqueous medium
 Structured stability
 Sizes about 50 to 200 nm
 Prolonged circulation in the blood
 Entrap hydrophobic and hydrophilic compounds and
charged particle
 Designed for drug delivery to brain tumor
Eg. Poly(ethylene glycol)-g-chitosan encapsulating all trans-
retinoic acid

12. Non-covalently connected polymeric micelles
 It is an novel block copolymer technique
 Obtained by self assemblage of homopolymer ,random
copolymer, graft copolymer
 Core and shell are non-covalently connected at their
homopolymer chain by H-bonding
 Eg. poly(4-vinyl pyridine) as a backbone and carbonyl
terminated polybutadiene as the graft

13. Types of polymer used
Micelles forming amphiphilic copolymer can be either
 Block copolymer (di,tri,tetra)
AB ,ABA
 Graft copolymer
AAAAAAAAA
B B
B B

14. TYPES EXAMPLE
BLOCK
POLYMER
(DI-BLOCK)
POLY(STYRENE)-B-POLY(ETHYLENEOXIDE)
POLY(ASPARTIC ACID)-B-POLYLACTIDE
PEG-B-POLY(ASPARTATE)
POLY(E-CAPROLACTONE)-B- POLY(METHACRYLIC ACID)
POLY(ETHYLENE OXIDE)-B-POLYCAPROLACTONE
BLOCK
POLYMER
(TRI-BLOCK)
POLY(E-CAPROLACTONE0-B-PEG-B-POLY(E-
CAPROLACTONE)
POLY(ETHYLENE OXIDE)-B-PLY(PROPYLENE OXIDE)-B-
PLOY(ETHYLENE OXIDE)
GRAFT
COPOLYMER
N-PTHLOYLCHITOSAN-G-POLYCAPOROLACTONE
STEARIC ACID-G-CHITOSAN

15. METHODS OF PRAPARATION
Can be prepared mainly by three common approach
 Direct dissolution
 Solvent casting technique
 Dialysis

16. Direct dissolution
 Direct dissolution of drug and copolymer in water
 It is simple technique
 Drug loading efficiency is low
Solvent casting
 Volatile organic solvent used to dissolve the copolymer &
drug
 After complete evaporation of solvent there is thin film
obtained
 Drug loaded micelles are obtained by reconstitution of
film in water

18. Dialysis
 Solution of drug and copolymer in organic solvent are
placed in dialysis bag and the solvent is exchanged
with water by immersing the bag into water inducing
micelle assembly.
 This method is suitable for loading of drug which has
poor solubility
 Suitable for core forming blocks are long & more
hydrophobic
 Dialysis process often take mare than 36 hours for
efficient drug loading

19. Lyophilization method
 Water tert. Butanol mixt. Is used for dissolving drug
as well as polymer and then solution is polymerised
 Drug loaded polymeric micelles obtained by
redispersing the lyophilized product in suitable vehicle
 It is simple and cost effective method

20. Characterization of polymeric micelles
CMC:
 It is the key parameter in the formation & the static
stability of polymeric micelles
 Con. of amphiphilic polmer in aqueous media
if , >cmc – exhist in t5he form of polymeric micelles
if , < cmc – micelles may collapse

21. CMC determination
 Surface tension measurement
 Chromatography
 Light scattering
 DSC
 Viscometry
 Pyren as fluorscent probe
Size & shape (geometry)
The polydispersity index of prepared structure is
obtained by examining the micellar solution using
light scattering techniques

22. Monodisperse micelles
 If produce blue color indicate good micellar
preparation
If produce white color indicate aggregation
 Scanning electron microcopy & transmission electron
microscopy has been used for size and shape
determination
In-vitro drug release behavior

23. Applications
Solubilization
 Solubilization process leads to enhance solubility of
water insoluble molecule in water
 Nan-osized polymeric micelles elevate GI uptake &
enhance its bioavailability

24. Example of improved solubility of drugs using
polymeric micellar system
DRUG AMPHIPHILIC POLYMER COMENT
Camptothesin Pluronic p-105,d-tocopherol
Peg 1000 succinate
Increased micellar
stability & bioavailability
Increased cytotoxicity
Docetaxel Polyethylene oxide-b-polystyrene
oxide
Increased solubility
Griseofulvin
Pacletaxel
EmBn (E-oxyethylene,B-
oxybutylene)
N-octyl-o-sulfate chitosan
Solubilization
independent of B block
length, when it exceeds
about 15B units
Improved bioavailability
& reduce cytotoxicity

25. Targetting delivery of drug
It is usually achieved by one of the following approaches
 Permeability enhancer
 Retention effect
 Stimuli sensitivity
internal : pH,enzymes
external : temp. ,light, ultrasound, magnetic field
 Liganding to micelle surface
 Immunomicelles

28. References
 Martins physical pharmacy & pharmacuetical sciences
maryland USA lippincott williams & wilkins:2007 pg
no. 469-97
 Moroi y.micelles: theorotical &applied aspects
springer international ed. New york:springer:2005 pg
no.41-50
 Jones mc ,leroux jc polymeric micelles: a new
generation of colloidal drug carriers. Eur j pharm
biopharm 1999 pg no.101-11

29. THANK YOU………..