Micelles? +revision qs

Question 1

reminder from SoM1»»

what are micelled?

Answer 1

core-shell nanostructures
that behave as lyophilic colloids

Question 2

what are micelles formed by?

Answer 2

amphiphilic (macro)molecules In a solvent that is selective for either moiety

Question 3

micelles could be soluble in water or not, depending on what?

Answer 3

orientation of the polar head and apolar tail

Question 4

how are surfactant micelles formed?

Answer 4

formed above the critical micelle concentration (CMC), once the surface is saturated

Question 5

how do surfactant micelles differ to polymeric micelles? in terms of formation

Answer 5

polymeric: formed by seld-assembly of amphiphilic block copolymers in solution (w hydrophilic block on outer surface and hydrophobic towards centre)
are bigger and more stable thus suited for DDS

surfactant: delf assembly of surfactant mols in soln.
hydrophilic head, hydrophobic tail. aq soln

Question 6

role of polymeric micelles?

Answer 6

Shield the drug from interaction with surrounding environment

Question 7

polymeric micelles can improve solubility of what?

Answer 7

hydrophobic drugs

Question 8

polymeric micelles form above a minimal conc and what techniques used to study their stability?

Answer 8

fluorescence

Question 9

what can effect efficient of polymeric micelles and drug delivery?

Answer 9

Different drug loading methods

Question 10

Micelles are internalised by endocytosis but can also dissociate and release the drug where?

Answer 10

outside of the cell

Question 11

What impact (if any) will increasing the length of the hydrophilic block on the CAC?

Answer 11

If the length of the hydrophilic block in an amphiphilic molecule is increased, it can ->

Increase CAC: longer hydrophilic block can-> increase CAC, as able to form stronger H bonds with water mols = more difficult for hydrophobic block to overcome the hydrophilic-hydrophilic interactions and form micelles.

Question 12

what is CAC?

Answer 12

Critical Aggregation Concentration and refers to the concentration of a surfactant or amphiphile at which it starts to form aggregates or micelles in a solution.

Question 13

Which formulation will have the fastest release: Micelles made of a semi-crystalline polymer or micelles made of an amorphous polymer?

Answer 13

Micelles made of an amorphous polymer as do not have a regular ordered structure, and molecular chains are randomly arranged = more susceptible to deformation and easier to penetrate by water molecules.

semi-crystalline polymers have ordered + disordered regions in structure. The ordered (crytalline) regions more tightly packed, and molecular chains are less mobile compared to the disordered regions = less permeable to water mols, and slower drug release

Therefore, amorphous polymers are often preferred for the formulation of fast-release drug delivery systems as they can rapidly swell and release the encapsulated drug or other molecules. However, the choice of polymer type depends on the specific application and the desired release profile.

Question 14

Which formulation will have the fastest release: Micelles made of a semi-crystalline polymer or micelles made of an amorphous polymer?

Answer 14

Micelles made of an amorphous polymer as do not have a regular ordered structure, and molecular chains are randomly arranged = more susceptible to deformation and easier to penetrate by water molecules.

semi-crystalline polymers have ordered + disordered regions in structure. The ordered (crytalline) regions more tightly packed, and molecular chains are less mobile compared to the disordered regions = less permeable to water mols, and slower drug release

Question 15

what type of polymers are often preferred for formulating fast release DDS?

Answer 15

amorphous polymers are often preferred for the formulation of fast-release drug delivery systems as they can rapidly swell and release the encapsulated drug or other molecules. However, the choice of polymer type depends on the specific application and the desired release profile.

Question 16

Explain how polyion complex micelles are formed.

Answer 16

Polyion complex micelles (PIC micelles) are self-assembled nanoparticles formed by electrostatic interactions between oppositely charged polyelectrolytes. The process of PIC micelle formation can be explained as follows:

Select opposite charged polyelectrolytes and mix. PIC micelles form: The polyelectrolyte complex self-assembles into a micelle-like structure due to the hydrophobic interactions between the nonpolar segments of the polyelectrolytes.

(The stability of the PIC micelles can be improved by cross-linking the polyelectrolyte complex or by modifying the surface of the micelles with hydrophilic molecules to prevent aggregation or precipitation.)

Question 17

What colloidal property can you use to differentiate between a unimolecular and micellar solution?

Answer 17

depends on solution properties on the concentration of the solute.

• unimolecular solution, properties such as its viscosity/ surface tension, do not significantly change with increasing solute concentration as solute is dissolved as individual molecules, and properties not influenced by intermolecular interactions. thus, conc of solute does not affect the colloidal properties of the solution.
• micellar solution, properties of solution change significantly with increasing solute conc due to formation of micelles- aggregates of amphiphilic molecules that have a hydrophobic core and a hydrophilic shell. As conc of solute increases, more and more micelles are formed -> changes in solution properties such as viscosity, surface tension, and conductivity, so concentration-dependent changes in the solution properties can be used to differentiate between a unimolecular and micellar solution.

For example, the critical micelle concentration (CMC) is the concentration at which micelles begin to form in a solution. Above the CMC, the concentration-dependent properties of the solution change significantly due to the formation of micelles, while below the CMC, the solution behaves as a unimolecular solution. Therefore, measuring the concentration dependence of properties such as surface tension or light scattering can help differentiate between unimolecular and micellar solutions.

Question 18

Explain the difference between thermodynamic and kinetic stability. Why are they both equally important?

Answer 18

Thermodynamic stability = system is in a state of minimum energy and is in a state of equilibrium. This state can be measured by equilibrium constants, Gibbs free energy, and enthalpy.

Kinetic stability = resistance of system to change over time, resistance to breaking down into its constituent parts or to converting into other species. requires a lot of energy input to initiate a transformation or degradation. This state can be measured by the rate of the reaction or process and activation energy.

both important in the design of chemical compounds and materials to ensure their long-term stability and performance.

Question 19

Explain how fluorescence can be used to determine the CAC. What properties must the fluorescent probe have to be used for this application?

Answer 19

to measure CAC, need to determine protein concentration were fluorescence signal becomes zero (the CAC).

• bright enough
• photostable
• excitable in cetrain wavelength range

Question 20

What is the most likely mechanism of uptake of passively targeted micelles in cancer cells?

Answer 20

Endocytosis and EPR effect!!

1)passively targeted micelles: micelles typically coated with hydrophilic polymers or other materials that help to increase their circulation time in the bloodstream and reduce their uptake by non-targeted tissues. bind to cancer cell membrane,and enter via endocytosis
2) leaky vasculature

Question 21

Explain the different ways how proteins can contribute to the premature drug release from micelles.

Answer 21

-Protein adsorption: When micelles are administered in vivo, they come into contact with various proteins in the biological fluids, such as serum albumin and fibrinogen. These proteins can adsorb onto the surface of the micelles, leading to changes in the surface properties of the micelles. This can result in a destabilization of the micelle structure, leading to premature drug release.

-Protein-induced aggregation: Proteins can also induce aggregation of micelles, leading to the formation of larger aggregates that are more prone to premature drug release. This can occur through protein-protein interactions or through the binding of proteins to the micelle surface.

-Enzymatic degradation: Proteins, such as enzymes, can also contribute to the premature drug release by degrading the micelle structure. For example, lipases can hydrolyze the lipid components of the micelles, leading to a destabilization of the micelle structure and premature drug release.

-Competitive displacement: Proteins that have a high affinity for the hydrophobic core of the micelles can displace the drug molecules from the core, leading to premature drug release. This can occur through competitive binding of the protein to the hydrophobic core of the micelles, which can result in the displacement of the drug molecules.

Question 22

PIC micelles advantages as a DDS?

Answer 22

• high stability in biological environments,
• improved solubility and bioavailability of hydrophobic drugs,
• specific targeting
  The size, shape, and surface properties of the PIC micelles can be tailored by selecting different polyelectrolytes and by modifying the micelle surface.