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………..