COLLOIDAL DISPERSION

MICELLES

Surfactants are amphiphilic molecules composed of a hydrophilic or polar moiety

known as head and a hydrophobic or nonpolar moiety known as tail.

Polar head portion

 The surfactant head can be charged (anionic or cationic), dipolar

(zwitterionic), or non-charged (nonionic).

 Sodium dodecyl sulfate (SDS), dodecyltrimethylammonium bromide

(DTAB), n-dodecyl tetra (ethylene oxide) (C12E4) and dioctanoyl

phosphatidylcholine (C8- lecithin) are typical examples of anionic, cationic,

nonionic and zwitterionic surfactants, respectively

Non-polar tail

 The surfactant tail is usually a long chain hydrocarbon residue and less often

a halogenated or oxygenated hydrocarbon or siloxane chain

MISCELLE FORMATION

1. A surfactant, when present at low concentrations in a system, adsorbs onto

surfaces or interfaces significantly changing the surface or interfacial free

energy.

2. Surfactants usually act to reduce the interfacial free energy, although there

are occasions when they are used to increase it

3. When surfactant molecules are dissolved in water at concentrations above

the critical micelle concentration (cmc), they form aggregates known as

micelles.

4. In a micelle, the hydrophobic tails flock to the interior in order to minimize

their contact with water, and the hydrophilic heads remain on the outer

surface in order to maximize their contact with water

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5. The micellization process in water results from a delicate balance of

intermolecular forces, including hydrophobic, steric, electrostatic, hydrogen

bonding, and van der Waals interactions.

6. The main attractive force results from the hydrophobic effect associated with

the nonpolar surfactant tails, and the main opposing repulsive force results

from steric interactions and electrostatic interactions between the surfactant

polar heads.

7. The determination of a surfactant cmc can be made by use of several

physical properties, such as surface tension (γ), conductivity (κ) – in case of

ionic surfactants, osmotic pressure (π), detergency, etc.

8. When these properties are plotted as a function of surfactant concentration

(or its logarithm, in case of surface tension), a sharp break can be observed

in the curves obtained evidencing the formation of micelles at that point

MICELLAR SOLUBILIZATION

1. Significance in pharmacy is their ability to increase the solubility of

sparingly soluble substances in water.

2. Solubilization can be defined as the spontaneous dissolving of a substance

by reversible interaction with the micelles of a surfactant in water to form a

thermodynamically stable isotropic solution with reduced thermodynamic

activity of the solubilized material.

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3. If we plot the solubility of a poorly soluble compound as a function of the

concentration of surfactant, as shown in Figure 4, usually what happens is

that the solubility is very low until the surfactant concentration reaches the

cmc. At surfactant concentrations above the cmc the solubility increases

linearly with the concentration of surfactant, indicating that solubilization is

related to micellization.

4. From the thermodynamic point of view, the solubilization can be considered

as a normal partitioning of the drug between two phases, micelle and

aqueous, and the standard free energy of solubilization (ΔGS º) can be

represented by the following expression

5. Accordingly, hydrophilic drugs can be adsorbed on the surface of the

micelle, drugs with intermediate solubility should be located in intermediate

positions within the micelle such as between the hydrophilic head groups of

PEO micelles and in the palisade layer between the hydrophilic groups and

the first few carbon atoms of the hydrophobic group, that is the outer core,

and completely insoluble hydrophobic drugs may be located in the inner

core of the micelle

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6. The existence of different sites of solubilization in the micelle results from

the fact that the physical properties, such as microviscosity, polarity and

hydration degree, are not uniform along the micelle.

7. The capacity of surfactants in solubilizing drugs depends on numerous

factors, such as chemical structure of the surfactant, chemical structure of

the drug, temperature, pH, ionic strength, etc.

8. Nonionic surfactants usually are better solubilizing agents than ionic

surfactants for hydrophobic drugs, because of their lower cmc values.

POLYMERIC MICELLES

1. Micelles prepared from block copolymers have attracted much attention

lately because of their better stability and biocompatibility

2. They are made from amphiphilic block copolymers with a large difference in

solubility between hydrophobic and hydrophilic portions.

3. Polymeric micelles generally have CMC values that are several orders of

magnitude lower than typical CMC values for surfactants.

4. As a result, polymeric micelles show enhanced stability and slower

dissociation at lower concentrations compared with surfactant micelles

5. Surface functionalization of a polymeric micelle can be easily performed by

chemically attaching a targeting moiety. Their low CMC values and lower

rate of dissociation also allow for prolonged release of entrapped drug.

6. Copolymer for micellization can be synthesized by using two or more

polymer blocks with contrasting solubility profiles. Poly (ethylene glycol)

(PEG) is the most commonly used hydrophilic (shell forming) block

7. Various molecular weights of PEG have been used for micelle preparation.

PEG is highly biocompatible and forms a highly stable shell to sterically

protect the hydrophobic core.

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8. It has also been shown to be efficient at escaping recognition by the

reticuloendothelial systems (RES), thereby extending the circulation time of

micelles in the blood

9. Moreover, PEG copolymers usually have a low polydispersity (Mw/Mn

ratio), which enables strict control of micelle size.

10. Surface functionalization of PEG micelles can be easily performed by

chemically linking a targeting moiety.

11. Thus, PEG micelles can be used for active targeting to cells and tissues.

12. Copolymers prepared by conjugating PEG with poly lactic acid (PLA) and

poly (ethylene oxide) (PEO) have been extensively investigated as micellar

vehicles

13. Other commonly used hydrophilic polymer blocks are poly (N-vinyl-2-

pyrrolidone) (PVP), poly (vinyl alcohol) (PVA), and poly (vinylalcohol-co-

vinyloleate). Triblock pluronic copolymers with an A-B-A structure

(Ethylene oxide)x-(Propylene oxide)y-(Ethylene oxide)x have been

extensively characterized

14. A variety of molecular weights and block lengths of Pluronic copolymers is

available commercially. These copolymers have shown promise for

delivering drugs and genes in vitro and in vivo.

POLYMER-LIPID MICELLES

 A variety of hybrid micelles with lipid core and hydrophilic polymer shell

has recently been investigated.

 Such micelles have shown good stability, longevity, and capability to

accumulate into tissues with damaged vasculature (EPR effect). Micelles

prepared by conjugation of PEG and phosphatidylethanolamine (PE) have

been studied for delivery of anticancer drug Camptothecin

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 Such conjugation resulted in formation of very stable micelles having low

toxicity and high delivery efficiency.

 PEG-PE conjugate form micelles with CMC in micromolar range, which is

about 100-fold lower than conventional detergent micelles.

 Polymer lipid micelles can be formed easily by spontaneous micellization in

aqueous media similar to surfactant and polymer micelles, and their size can

be tailored by varying the molecular weight of the conjugate.

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