Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients

Figures & data

Figure 1 Chemical structure of lactone and carboxylate forms of 9-nitrocamptothecin showing their equilibrium reaction, (A) lactone form, (B) carboxylate form.

Figure 2 Scanning table electron micrograph of 9-nitrocamptothecin nanoparticles.

Figure 3 Size distribution of 9-NC nanoparticles.

Table 1 Results of drug loadings according to amount of polymer (n = 3)

Formulation	Polymer (mg)	PVA (mg)	Int. phase (mL)	Ext. phase (mL)	EE (%)
1	50	50	12	22	13.5 ± 3.7
2	100	50	12	22	15.6 ± 2.7
3	125	50	12	22	22.3 ± 3.4
4	150	50	12	22	28.7 ± 2.3
5	165	50	12	22	45.3 ± 2.9
6	180	50	12	22	33.3 ± 2.1
7	200	50	12	22	31.3 ± 4.8
8	250	50	12	22	28.9 ± 3.1
9	300	50	12	22	26.5 ± 1.9

Abbreviations: EE, entrapment efficacy; PVA, polyvinyl alcohol.

Table 2 Results of drug loadings according to amount of surfactant (n = 3)

Formulation	Polymer (mg)	PVA (mg)	Int. phase (mL)	Ext. phase (mL)	EE (%)
1	165	0	12	22	–
2	165	25	12	22	18.2 ± 5.8
3	165	35	12	22	23.4 ± 6.2
4	165	50	12	22	45.3 ± 2.9
5	165	75	12	22	28.8 ± 4.9
6	165	100	12	22	15.2 ± 4.2

Abbreviations: EE, entrapment efficacy; PVA, polyvinyl alcohol.

Table 3 Results of drug loadings according to internal phase volume (n = 3)

Formulation	Polymer (mg)	PVA (mg)	Int. phase (mL)	Ext. phase (mL)	EE (%)
1	165	50	5	22	–
2	165	50	10	22	35.89 ± 4.2
3	165	50	12	22	45.3 ± 2.9
4	165	50	15	22	23.4 ± 4.7
5	165	50	25	22	11.7 ± 4.3

Table 4 Results of drug loadings according to amount of external volume (n = 3)

Formulation	Polymer (mg)	PVA (mg)	Int. phase (mL)	Ext. phase (mL)	EE (%)
1	165	0	12	5	–
2	165	25	12	10	10.1 ± 6.9
3	165	35	12	20	13.1 ± 5.2
4	165	50	12	22	45.3 ± 2.9
5	165	75	12	25	38.3 ± 7.4
6	165	100	12	30	30.0 ± 8.6

Figure 4 DCS thermograms obtained for A) 9-NC, B) Physical mixture, C) Nanoparticles, D) Copolymer.

Figure 5 XRD patterns. A) 9-NC, B) Copolymer, C) Nanoparticle, D) Physical mixture of drug and copolymer.

Figure 6 9-NC release curve from optimum formulation of PLGA-PEG and PLGA nanoparticles.

Table 5 Results of release kinetics according to zero order, first order, and Higuchi equations

K^ah μg/h^0.5	Regression coefficient (R^2)
	Higuchi	First order	Zero order
4.351	0.989	0.922	0.896