Environmental Engineering Reference
In-Depth Information
16.3 Preparation of Drug-Loaded Polymer Micelles
In order to incorporate or solubilize one or more drugs physically into the block
copolymer micelle, various methods have been proposed [ 32 ]:
(a) Stirring. A drug is added to an aqueous solution of a block copolymer, and
stirred for 2-24 h to obtain micelles containing the physically entrapped drug.
(b) Heating. A drug and a block copolymer are dissolved in an organic solvent and
the solvent is evaporated off at an elevated temperature (40-80 C under a
nitrogen atmosphere or by rotary evaporator under vacuum). The resulting
mixture is kept at a temperature of 20-80 C, preferably at 40-70 C, for 2 h.
Then, warm water (40-70 C) is added thereto, and the mixture is stirred until
a polymeric micelle containing drug is formed.
(c) Ultrasonic Treatment. A mixture of a drug and an aqueous solution of a block
copolymer is subjected to ultrasonic treatment for a period ranging from about
1 s-1 h and then stirred at room temperature to obtain micelles containing
the drug.
(d) Solvent Evaporation. A drug is dissolved in a water-immiscible organic
solvent, for example, dichloromethane, chloroform, and the like, and then
added to an aqueous solution of a block copolymer. Subsequently, the organic
solvent is slowly evaporated off at 25-40 C while stirring, and then filtered to
remove undissolved drug. Drug along with the polymer is dissolved in a water-
immiscible organic solvent like tetrahydrofuran, chloroform, acetone, or a
mixture of solvents like chloroform and ethanol, and this solution is slowly
added to the distilled water under vigorous stirring to form an emulsion with
an internal organic phase and continuous aqueous phase, which rearranges the
polymer to form micelles. Sometimes surfactants like polyvinyl alcohol are
used in aqueous solution. This emulsion is then kept open to air with stirring so
as to evaporate all the organic solvent.
(e) Dialysis. A drug and a block copolymer are dissolved in a water-miscible
organic solvent. The solution is dialyzed against a buffer solution and then
against water for the removal of organic solvent. In the dialysis method,
suitable water-miscible organic solvents for dissolving drugs are selected
from the group consisting of acetonitrile, dimethylformamide, dimethyl-
sulfoxide, dioxane, dimethylacetamide, and the like.
(f) Solid dispersion method. In this method, drug along with the polymer is
dissolved in the organic solvent, and a solid polymer matrix is obtained after
the evaporation of solvent under reduced pressure. Drug-loaded PMs are
obtained after the addition of water to the preheated polymer matrix [ 33 ].
(g) Microphase separation method. In this method the drug and polymer are
dissolved in (organic solvent) tetrahydrofuran, and the solution is added
dropwise in water under magnetic stirring. PMs are formed spontaneously,
and drugs are entrapped in the inner part of the micelles. Organic solvent is
removed under
reduced pressure, and a blue-colored PM solution is
formed [ 34 ].
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