4. Introduction to Micelle
• Micelles are aggregates of colloidal particles which
have both hydrophobic and hydrophilic parts.
• Micelles are amphiphilic molecules, i.e., they
comprise both hydrophilic (forming the corona/shell)
and hydrophobic (forming the core) parts.
• A typical micelle has a spherical structure (5-100
nm).
• Example: Polyethylene glycol (PEG)‐polylactic acid,
PEG‐PLGA, polyethylene oxide‐poly(propylene
Fig 1. Micelle structure
5. Micelle Formation
• Critical Micelle Concentration (CMC): The lowest
concentration at which a micelle appears.
• In water, polymers at low concentration form only
single chains.
• With the increase in concentration, it reaches CMC
where polymer chains start to associate which
further assembles and form micelles structure in
such a way that the hydrophobic part forms the
central core and hydrophilic portion forms the shell.
This is called the self-assembly of micelles.
Fig 2. Micelle formation in
water.
6. Assembly: Micelle vs Liposome
• Micelle comprises a single fatty acid tail & thus isn’t a
bulky molecule. Therefore, their tails can easily and
steadily fit into the interior space of the micelle
structure.
• The double fatty acid tail structure of liposome, makes
it a bulkier lipid molecule and will spontaneously
rearrange themselves in an aqueous solution to form
a bilayer structure.
• This is because the larger non-polar tails of these
lipids are too large to fit into the limited space of the
micelle.
Fig 3. a) Micelle structure; b)
Lipid bilayer structure
7. Micelle Drug Delivery System
• Step 1: Prepare micelle NPs
through self-assembly of the
micelle in water.
• Step 2: Once the micelles are
formed, transfer them to a solution
comprising a drug solution.
• Step 3: The hydrophobic drug gets
entrapped in the hydrophobic core
of the micelle.
Fig 4. Formation of Micelle Drug Delivery System
9. Applications of Micelle Drug Delivery
Systems
• Drug carriers for hydrophobic drugs.
• Cancer therapy.
• Gene delivery
• Intracellular Protein Delivery for protein-based therapeutics.
12. Fig 5. Schematic illustration of the coordination interaction-mediated high drug loading
[Ref (Wu et. al., 2020)]
13. Drug-loaded Nanomicelles
• A di-block copolymer mPEG113-b-PHEA21 was
first synthesized and then the PHEA block was
modified with 9-10 phenylboronic acid (PBA)
residues to obtain the amphiphilic copolymer
PPBA.
• Drugs encapsulated: Doxorubicin (DOX) and
irinotecan (IR).
• Drug-loaded micelles prepared:
1. IR-loaded PPBA (PPBA-I),
2. DOX-loaded PPBA (PPBA-D)
3. (DOX + IR)-co-loaded-PPBA (PPBA-DI)
4. DOX-loaded PCBZ (PCBZ-D) micelles
Fig 6. Size distribution of PPBA-D,
PPBA-I, and PPBA-DI micelles using
dynamic laser scattering (DLS) [Ref
(Wu et. al., 2020)].
14. Drug Loading Efficiency (DLE)
• Drug loading efficiency, defined as the ratio of the amount of drug in the nanoparticle to
the total amount of drug applied in the formulation of the nanoparticles.
• When the polymer: DOX: IR weight ratio was maintained at 2:1:1, DLE was found to be
maximum.
• Drug loading efficiency (%):
• DOX: 96.4 %
• IR: 93.6 %
• This ultra-high drug encapsulation efficiency is extremely promising for in vivo release.
15. In vitro Drug Release
• DOX and IR from PPBA-DI micelles were evaluated
in the presence or absence of 100 μM H2O2.
• Release of DOX from PPBA-DI micelles (48 h
incubation):
74% of the loaded DOX was released in the
presence of H2O2.
25% of the loaded DOX was released in the
absence of H2O2.
• Release of IR from PPBA-DI micelles (48 h
incubation):
80% of the loaded DOX was released in the
presence of H2O2.
Fig 7. Cumulative release of DOX (a and c) and IR (b
and d) from PPBA-DI micelles (a and b) or PCBZ-DI
micelles (c and d) in the presence or absence of
H2O2 [Ref (Wu et. al., 2020)].
16. In vitro Cytotoxicity Study
• Cytotoxicity of the blank copolymer micelles was evaluated by the MTT assay.
• Cell Viability Tests were performed using the following cell lines:
LLC – Lewis Lung Carcinoma cell line
SKOV-3 – Human Ovarian Cancer cell line
NIH-3T3 - Normal fibroblast cell line
17. In vivo anti-tumor Efficacy
• In vivo anti-tumor efficacy of PPBA-DI micelles was investigated in LLC xenograft
tumor-bearing mice.
• The PPBA-DI micelle showed the best tumor inhibition efficiency.
• Almost complete retardation of tumor growth during the 16-day observation period,
outperforming micelles encapsulating a single chemo-drug or free-drug combination
(free DOX + IR).
18. Conclusion
• A precise co-delivery micellar system with two different chemo-drugs by the introduction
of strong donor-receptor coordination between the drugs and the polymeric nanocarriers
was developed.
• The optimized PPBA-DI micelles possessed robust stability, suitable size distribution,
ultra-high drug loading capacity, and desired biocompatibility.
• PPBA-DI micelles could be efficiently internalized by LCC cells and provoke a synergistic
anti-cancer effect against LLC tumors both in vitro and in vivo.
• Therefore, such a co-delivery strategy with high drug loading and a precisely adjustable
drug ratio holds great promise for combination anti-cancer chemotherapy.
26. References
• Kapare HS, Metkar SR. Micellar drug delivery system: a review.
Pharmaceutical resonance. 2020;2(2):21-6.
• Bose A, Roy Burman D, Sikdar B, Patra P. Nanomicelles: Types,
applications in drug delivery. IET nanobiotechnology. 2021
Paper Presentation:
• Wu Y, Lv S, Li Y, He H, Ji Y, Zheng M, Liu Y, Yin L. Co-delivery
precisely controlled, high drug loading polymeric micelles for
therapy. Biomaterials science. 2020;8(3):949-59.
