This document discusses the use of polymer micelles for targeted drug delivery. Polymer micelles are nano-sized particles composed of amphiphilic block copolymers with both hydrophobic and hydrophilic blocks that can self-assemble in water. They are promising drug carriers as they can solubilize hydrophobic drugs and extend circulation time. Two common preparation methods are direct dissolution and solvent evaporation. Drug release can be triggered by internal factors like pH or temperature changes at the target site. Important parameters for characterization include encapsulation efficiency and loading capacity. Polymer micelles show potential for applications in cancer therapy and other diseases.

1. Target Drug Delivery Through Polymer Micelle
Bangladesh University of Engineering and Technology
Submitted By
Anwarul Azim Akib
Student ID: 0419032706, Session: April 19
Course Code:6016
Department of Chemistry

2. Contents
 Polymer micelle
 Use of polymer micelle as drug carrier
 Preparation of polymer micelle
 Factors governing drug release
 Important parameters
 References

3. What is polymer micelle ?
Polymeric micelles are the self assembled Nano-sized colloidal particles
which are made up of amphiphilic block copolymers i.e. polymers
consisting of hydrophobic block and hydrophilic block. These
polymeric micelles possesses the particle sizes range between 10–100
nm which making them considerably smaller than phospholipids
vesicles (liposomes). These polymeric micelles Nano carriers have
applications in drug delivery primarily such as
 anticancer therapy,
 to the brain to treat neurodegenerative diseases,
 antifungal agents,
 stimuli-responsive Nano carriers for drug and
 gene delivery, ocular drug delivery.

4. Why we use polymer micelle as drug carrier ?
 Polymeric micelles have gathered considerable attention in the field of
drug and gene delivery due to their excellent biocompatibility, low
toxicity, enhanced blood circulation time, and ability to solubilize a
large number of drugs in their micellar core.
 In general, 40% of drugs have low solubility (e.g. peptides, proteins
and genes drug). Low solubility limits the drug dissolution rate, which
frequently results in low bioavailability of the orally administered drug.
 The major advantage of polymer micelles is its ability to solubilize
poorly soluble drugs. Once its solubility get increased, the absorption
of drug in body will also be enhanced which results in increased
bioavailability.

5. How we prepare polymer micelle ?
 In aqueous medium amphiphilic block copolymers can principally
self assemble into spherical micelles, worm-like or cylindrical
micelles, and polymer vesicles or polymersomes.
 By using the self-assembly of block copolymers there are two general
methods for the preparation of polymeric micelles. One is the direct
dissolution method or the organic solvent-free method and the other
is the solvent evaporation or solution-casting technique or ‘solvent-
switch’ method.

6. Self assembly of di-block co-polymer
Figure 1: Self assembly of di-block co-polymer

7. Direct Dissolution method
 It involves direct dissolution of the amphiphilic copolymer and
drug in water for preparing drug-loaded polymeric micelles.
 Water is mandatory to allow for self-assembly.
 But low drug loading is the disadvantage of this method.
 To enhance drug loading, this technique can be combined with an
increase in temperature or alternately before the addition of
copolymer, a thin evaporated film of drug can be prepared.

8. Solvent evaporation or solution-casting method
 Most amphiphilic block copolymers are not directly soluble
in water.
 In this method, a volatile organic solvent is employed to
dissolve the block copolymer and the drug .
 A thin film of copolymer and drug is obtained after the
solvent is removed by evaporation.
 Drug-loaded polymeric micelles are obtained by
reconstitution of film with water.
 Micelles from such copolymers have more potential to
solubilize large amounts of poorly water-soluble drugs.

9. Factors Governing Micelle formation
 Micelle formation in aqueous solution is mainly governed by the effective
interaction between the hydrophobic parts of the surfactants.
 The assembly formation starts only when a certain minimum concentration is
crossed by the amphiphilic molecules, called as critical micelle
concentration.
 The major driving force behind self-association is the decrease of free energy
of the system.
 Decrease in energy of the system is a result of removal of hydrophobic
fragments from the aqueous surroundings with the formation of a micelle
core stabilized with hydrophilic blocks exposed into water.
 The change in free energy for the micellization process is described as:
∆G 𝑚𝑖𝑐 = RT 𝑙𝑛(CMC)
where R is the gas constant, T is the temperature of the system and CMC is the
critical micelle concentration .

10. Continue…
 Another main factor governing the morphology of micelles is the
hydrophilic–hydrophobic balance of the block copolymer defined by
the hydrophilic volume fraction, f.
 For amphiphilic block copolymers with value of f nearly 35%, polymer
vesicles are formed, whereas, for f value more than 45%, spherical
micelles are formed from self-assembly.
 The hydrophilic weight ratio (the weight of the hydrophilic block
divided by the weight of the copolymer) is a good approximation of
the hydrophilic volume ratio.
 Other factors of importance are the conditions of the system as
solvent, concentration of amphiphiles, temperature, etc.

11. Relation between hydrophobic part of polymer
micelle with critical solution concentration
 CMC, is defined as the minimum concentration necessary for an
amphiphilic material to be able to form Nano micelles by self-assembly,
in aqueous environments.
 Critical micelle concentration (CMC), which depends on the
hydrophilic/hydrophobic balance of the block copolymer as well as the
chemical characteristics and molecular weight of the blocks. It has been
observed that the higher the hydrophobic chain the lower is the polymer
concentration needed for micelle formation.

12. Polymers use for for Drug delivery system
 Polymers that are used in the formation of polymeric micelles must be an FDA
approved devices;
 These requirements limit the choice for the various blocks.
 For hydrophilic segment Poly (ethylene glycol) (PEG), poly (N-vinyl-2-pyrrolidone)
(PVP) are widely used polymer because they are inexpensive, non biodegradable in
nature, and has low toxicity. For this reason they can easily removed from the body
through the excretion pathway.
 Polylactide (PLA), poly (lactide-co-glycolide) (PLGA), poly (Ɛ-caprolactone)
(PCL), poly (lactide-cocaprolactone), poly(p- dioxanone ), poly( pdioxanone -co-
lactide), poly(p-di oxano neco caprolactone), poly(3-hydroxybutyrate), and
polyorthoester, are widely employed hydrophobic blocks.
 Other biodegradable polymers such as polyanhydride, derivatives of poly(amino
acid) and non-degradable polymers like poly( alkylacrylate ) are also patented
hydrophobic segments.

13. Factors governing drug release
 The drug should be released only after the polymeric
micelles accumulate at the targeted tissue, by means of
some internal trigger such as pH, particular enzyme, etc. or
by an external trigger including temperature, light,
ultrasound or magnetic field.

14. pH sensitive drug release
The micelle are relatively stable at normal tissue and blood
where pH is around 7.4, but start to release drug at acidic
condition. The pH value of most solid tumor ranges from
pH 6.5 to 7.2, which is less than normal tissue. Differences
in pH between normal tissue and the tumor tissue can be
internal stimulus for triggered drug release.

15. Continue….

16. Continue….
Table 1: Linearity Result of Amlodipine Besylate Sample

17. Thermal sensitive drug release
 Generally, a LCST is a critical temperature below which all
compositions of a mixture are miscible and thus exist in a single
phase . If the temperature of a mixture is raised above the LCST
of one of its components, that component undergoes thermally
induced phase separation by either nucleation and growth or by
spinodal decomposition (SD).
 Below the LCST the polymer is hydrated due to the formation of
hydrogen bonds between water and polymer molecules, whereas
above this temperature the hydrogen bonds between the polymer
chains and water are disrupted, rendering the polymer
hydrophobic, leading to its collapse or precipitation.

18. Figure3: Thermal behavior of drug loaded polymer micelle
.
Continue…

19. Continue…
 Lower critical Solution Temperature of these polymer micelle
should around the normal body temperature (37℃)
 In-virto drug release can be determine under physiological
condition (PBS, pH 7.4) at 37℃ (below the LCST) and 41℃
(above the LCST) respectively. Theoretically the LCST should
increase up to 45.1℃ when the drug release 100% for all sample.

20. Important Parameters
 Encapsulation efficiency (EE) : Encapsulation efficiency is the
percent of drug that entrapped into the micelle or nanoparticle.
% of encapsulation efficiency =
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛 𝑚𝑖𝑐𝑒𝑙𝑙𝑒
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑓𝑒𝑑 𝑖𝑛𝑖𝑡𝑖𝑎𝑙𝑙𝑦
× 100
 Loading capacity (LD) : Loading capacity is the amount of drug
loaded per unit weight of the nanoparticles, indicating percentages of
mass of nanoparticles that is due to the encapsulated drug.
% of Drug loading capacity =
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛 𝑚𝑖𝑐𝑒𝑙𝑙𝑒
𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑚𝑖𝑐𝑒𝑙𝑙𝑒
× 100

21. References
[1] Ren Zhong Xiao,Zhao wu Zeng, Guang Lin Zhou1, Jun Jie wang1,Fan Zhu Li,An
Ming wang, Recent advances in PeG–PLA block copolymer nanoparticles, International
Journal of Nanomedicine 2010:5 1057–1065.
[2] Marina Talelli1,Wim E Hennink, Thermosensitive polymeric micelles for
targeteddrug delivery, Nanomedicine (2011) 6(7), 1245–1255.
[3] Zhang H, Xia H, Wang J, Li Y. High intensity focused ultrasoundresponsive release
behavior of PLA-b-PEG copolymer micelles. J Control Release. 2009;139(1):31–39.
[4] Vila A, Sánchez A, Évora C, Soriano I, McCallion O, Alonso MJ. PLAPEG particles
as nasal protein carriers: the influence of the particle size. Int J Pharm. 2005;292(1–
2):43–52.
[5] Matsumoto J, Nakada Y, Sakurai K, Nakamura T, Takahashi Y.Preparation of
nanoparticles consisted of poly(L-lactide)-poly(ethyleneglycol)-poly(L-lactide) and their
evaluation in vitro. Int J Pharm. 1999;185(1):93–101

22. Thank you