153
deacetylated, and hydroxypropyl cellulose MW = 370,000 g/
mol were purchased from Aldrich. Methyl methacrylate (99%
MMA) was purchased from Aldrich and purified by distillation
before use. Succinic anhydride was purchased from SigmaAldrich and purified with recrystallization. Daunorubicin
hydrochloride (DNR) was provided by Pharmacia & Upjohn
and used as received.
2. Solvents: Deionized and distilled water was used in all
processes.
3 Methods
The synthetic procedure of the PMMA@HPC@CS@CH microspheres consists of four steps: (a) synthesis of PMMA nanospheres
(NCs), (b) synthesis of PMMA@HPC NCs, (c) synthesis of
PMMA@HPC@CS NCs, and (d) synthesis of PMMA@HPC@CS@
CH NCs (see Note 1, Fig. 1).
Initially, PMMA nanospheres are synthesized by random radical emulsion polymerization of methyl methacrylate:
1. In a round-bottom flask, add:
(a) 28 mL H 2 O (see Note 2).
(b) 3 mL Methyl methacrylate (MMA) (see Note 3).
(c) 0,015 g KPS initiator (K 2 S 2 O 8 , t 1/2 = 8 h at 70 °C).
2. Leave the reaction overnight for completion.
3. Centrifuge the milky emulsion for nanospheres’ isolation (see
Note 4).
Continuously, PMMA nanospheres are used as core for the
polysaccharides’ coating by sequential deposition technique of
cortices (layer-by-layer deposition).
Forming of the first layer by deposition of hydroxypropyl cellulose (HPC):
4. Dissolve 0.4 g of hydroxypropyl cellulose (HPC) in 50 mL
acidic solution (see Note 5).
5. Add and disperse 0.4 g of PMMA spheres in 50 mL aqueous
solution (see Note 6).
6. Leave the mixture under stirring for 24 h at 50 °C.
7. Centrifuge the emulsion (see Note 7).
Forming of the second layer by succinic acid-modified cellulose
(CS, see Note 8):
8. Dissolve 0.1 g of cellulose succinate in 50 mL of basic solution
(see Note 6).
9. Add and disperse 0.4 g of HPC-coated spheres in 50 mL of
acidic aqueous solution (see Note 5).
3.1 Synthesis
of PMMA@HPC@CS@
CH Nanospheres (NCs)
Design of Drug Delivery Systems Based on Polysaccharides
deacetylated, and hydroxypropyl cellulose MW = 370,000 g/
mol were purchased from Aldrich. Methyl methacrylate (99%
MMA) was purchased from Aldrich and purified by distillation
before use. Succinic anhydride was purchased from SigmaAldrich and purified with recrystallization. Daunorubicin
hydrochloride (DNR) was provided by Pharmacia & Upjohn
and used as received.
2. Solvents: Deionized and distilled water was used in all
processes.
3 Methods
The synthetic procedure of the PMMA@HPC@CS@CH microspheres consists of four steps: (a) synthesis of PMMA nanospheres
(NCs), (b) synthesis of PMMA@HPC NCs, (c) synthesis of
PMMA@HPC@CS NCs, and (d) synthesis of PMMA@HPC@CS@
CH NCs (see Note 1, Fig. 1).
Initially, PMMA nanospheres are synthesized by random radical emulsion polymerization of methyl methacrylate:
1. In a round-bottom flask, add:
(a) 28 mL H 2 O (see Note 2).
(b) 3 mL Methyl methacrylate (MMA) (see Note 3).
(c) 0,015 g KPS initiator (K 2 S 2 O 8 , t 1/2 = 8 h at 70 °C).
2. Leave the reaction overnight for completion.
3. Centrifuge the milky emulsion for nanospheres’ isolation (see
Note 4).
Continuously, PMMA nanospheres are used as core for the
polysaccharides’ coating by sequential deposition technique of
cortices (layer-by-layer deposition).
Forming of the first layer by deposition of hydroxypropyl cellulose (HPC):
4. Dissolve 0.4 g of hydroxypropyl cellulose (HPC) in 50 mL
acidic solution (see Note 5).
5. Add and disperse 0.4 g of PMMA spheres in 50 mL aqueous
solution (see Note 6).
6. Leave the mixture under stirring for 24 h at 50 °C.
7. Centrifuge the emulsion (see Note 7).
Forming of the second layer by succinic acid-modified cellulose
(CS, see Note 8):
8. Dissolve 0.1 g of cellulose succinate in 50 mL of basic solution
(see Note 6).
9. Add and disperse 0.4 g of HPC-coated spheres in 50 mL of
acidic aqueous solution (see Note 5).
3.1 Synthesis
of PMMA@HPC@CS@
CH Nanospheres (NCs)
Design of Drug Delivery Systems Based on Polysaccharides