Polymeric micelles Flashcards
What are micelles?
A micelle is an aggregate of amphiphilic molecule dispersed in a liquid colloid.
The amphiphilic polymer is composed of hydrophilic head and hydrophobic tail.
In aqueous environment, the amphiphilic polymer molecules aggregate into a spherical core-shell structure, with the hydrophilic heads in contact with the surrounding water forming the shell, sequestering the hydrophobic tail region in the core of the micelles.
What is solubilisation like for micelles?
Drug entrapment in the hydrophobic core enhance the solubilisation of poorly soluble compounds.
Solubilisation is either through physical or chemical encapsulation.
Physical encapsulation:
Does not need chemical modification.
Lower drug loading compared to chemical encapsulation.
Drug release either through diffusion or upon disassociation of the micelle structure.
Chemical encapsulation:
Drug chemically conjugated to hydrophobic block (pro-drug).
Higher drug loading compared to physical encapsulation.
Useful for targeting.
Provides sustained drug release.
What is significant about the size of micelles?
Small enough to penetrate capillaries within the body; effective tissue distribution.
Intact micelles are big enough to avoid renal clearance
Renal clearance happen when micelles fall apart either through biodegradation of the unimers or through simple dilution of the micelle into unimers.
Better retention in solid tumours of high permeability and poor lymphatic drainage. Thus, provides good platform of chemotherapeutic delivery.
How are micelles released?
Polymeric micelles have the ability to slowly release a molecule over time.
Micelles should be stable to dilution while circulating in the bloodstream to secure slow controlled release.
How are micelles formed?
At very low concentrations, the polymers only exist as single soluble chains.
As the concentration increases to reach a critical value called the critical micelle concentration (CMC), polymer chains start to associate to form micelles in such a way that the hydrophobic part of the polymer will avoid contact with the aqueous media in which the polymer is diluted.
How are micelles classified?
Polymeric micelles are classified according to their hydrophobic blocks into three main classes: poly(propylene oxide), poly(L-amino acid)s and poly(ester)s.
Poly(propylene oxide) - also known as poloxamers and pluronics.
What are the roles of pluronic L61 and pluronic F127?
Pluronic L61 - enhance cellular uptake and retention of DOX through inhibition of the drug efflux protein P-gp expressed on cell surfaces.
Pluronic F127 - improve solubilisation of both DOX and the hydrophobic L61 component.
What are the advantages and disadvantages of poloxamers?
Advantages:
Water soluble - can form micelles spontaneously upon direct addition to water, allowing for simple preparation, can be used for IV administration.
Inhibit P-glycoprotein (P-gp) and multidrug-resistance protein, which may serve to enhance the activities of chemotherapeutic agents and blood brain barrier uptake of drugs.
Solubilisation of insoluble drugs.
Disadvantages:
The core-forming block material is fixed limiting the range of drug molecules that are compatible with poloxamer micelles.
What are the advantages of Poly(L-amino acid)s?
Main advantage is that the core is formed of amino acids (AA).
20 AA-flexibility of design & great versatility for drug delivery.
Natural AA-biodegradable (enzymatic) & biocompatible.
What are the advantages and disadvantages of polyesters?
Advantages:
Main advantage is that the core is formed of esters.
Susceptible to hydrolysis, resulting in degradation to non-toxic species (biodegradable & biocompatible).
Disadvantages:
Not as amenable to chemical modifications as the poly(amino acid)s, thus used mainly for physical encapsulation of drugs.
