Polymeric micelles
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Transcript of Polymeric micelles
A SEMINAR ON POLYMERIC MICELLES
PRESENTED BYMR. KIRAN N. PATANGEM.PHARM II SEMISTER
DEPT. OF PCEUTICAL SCIENCESRTMNU,NAGPUR
POINTS TO BE COVERED……….INTRODUCTIONMECHANISM OF MICELLIZATIONFACTORS AFFECTING THE PROCESS OF
MICELLES FORMATIONWHY POLYMER MICELLSES ARE ATTRACTIVETYPES OF POLYMERIC MICELLESTYPES OF POLYMER USEDMETHODS OF PREPARATION CHARACTERIATION OF POLYMERIC
MICELLESAPPLICATIONS
INTRODUCTIONMICELLES: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
Polymeric micellesThis are self assembled colloidal particle with
hydrophobic core and hydrophilic cellIt 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
Machanisnm of micellization Amphiphilic molecule + solvent
Self association of amphiphilic molecules
Polymeric micelles
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 .
Factors affecting process of micelles formation
Molecular wt. of monomerAggregation no.Proportion of hydrophobic and hydrophilic chain
lengthPreparation processCMC
WHY POLYMERIC MICELLES ARE ATRRACTIVE
Polymeric micelles have gathered attention in drug & protein delivery due to :
BiocompatibilitySolubilization of hydrophobic moeities in micellar coreMore stable toward dilution & hence exhibit minimal
cytotoxicityEnhanced blood circulation time suitable for i.v.
administration drug delivery systemSmart or intelligent drug carriers
Types of polymeric micelles
Based on intermolecular forces governing the segregation of the core segment from aqueous environment.
ConventionalPoly-ion complex micellesNon-covalently connected polymeric micelles
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
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
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
Types of polymer usedMicelles forming amphiphilic copolymer can be either
Block copolymer (di,tri,tetra)
AB ,ABA
Graft copolymer
AAAAAAAAA
B B
B B
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
METHODS OF PRAPARATION
Can be prepared mainly by three common approach
Direct dissolution
Solvent casting technique
Dialysis
Direct dissolution Direct dissolution of drug and copolymer in water It is simple technique Drug loading efficiency is low
Solvent castingVolatile organic solvent used to dissolve the copolymer &
drugAfter complete evaporation of solvent there is thin film
obtained Drug loaded micelles are obtained by reconstitution of
film in water
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
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
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
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
Monodisperse micelles
If produce blue color indicate good micellar preparation
If produce white color indicate aggregationScanning electron microcopy & transmission electron
microscopy has been used for size and shape determination
In-vitro drug release behavior
Applications
Solubilization
Solubilization process leads to enhance solubility of water insoluble molecule in water
Nan-osized polymeric micelles elevate GI uptake & enhance its bioavailability
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 & bioavailabilityIncreased 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 unitsImproved bioavailability & reduce cytotoxicity
Targetting delivery of drug
It is usually achieved by one of the following approaches Permeability enhancer Retention effectStimuli sensitivity
internal : pH,enzymes
external : temp. ,light, ultrasound, magnetic fieldLiganding to micelle surfaceImmunomicelles
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
THANK YOU………..