Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

Figures & data

Figure 1 Poly(d,l-lactide-co-glycolide) hydrolysis.

Figure 2 Structures of A) triamcinolone acetonide and B) polyethylene glycol ether.

Table 1 Selected parameters and their levels for experimental design

Parameters	Level
	1	2	3
A) TR% (w/w)	5	10	15
B) Nano HA% (w/w)	1	3	5
C) GL% (w/w)	1	3	5

Abbreviations: TR, triamcinolone acetonide; HA, hydroxyapatite; GL, polyethylene glycol ether.

Table 2 L₉ orthogonal array

Run #	Parameter levels
	A	B	C
1	1	1	1
2	1	2	2
3	1	3	3
4	2	1	2
5	2	2	3
6	2	3	1
7	3	1	3
8	3	2	1
9	3	3	2

Figure 3 Triamcinolone acetonide release kinetics in poly(d,l-lactide-co-glycolide) in phosphate buffer.

Table 3 Cumulative release after 1.5 days

Run #	% response			Average (%)	SD
	1	2	3
1	4.5	4.0	4.1	4.2	0.3
2	3.9	4.1	4.7	4.2	0.4
3	4.7	4.6	4.2	4.5	0.3
4	2.0	2.3	2.0	2.1	0.2
5	2.2	2.3	2.2	2.2	0.1
6	2.3	2.5	2.4	2.4	0.1
7	1.5	1.6	1.6	1.5	0.1
8	1.4	1.5	1.3	1.4	0.1
9	1.2	1.5	1.3	1.3	0.2

Figure 4 Hydroxyapatite nanoparticles.

Figure 5 Cumulative triamcinolone acetonide release kinetics in poly(d,l-lactide-co-glycolide)-hydroxyapatite in phosphate buffer.

Table 4 ANOVA for cumulative release after 1.5 days

Parameters	DOF	Sum of squares	Variance	F-ratio	Pure sum	Percent (%)
A) TR% (w/w)	2	39.6	19.8	450.0	39.5	96.9
B) Nano HA% (w/w)	2	0.1	0.0	1.0	0.0	0.0
C) GL% (w/w)	2	0.2	0.1	2.3	0.1	0.3
Other/error	20	0.9	0.0			2.8
Total	26	40.8				100.0

Abbreviations: TR, triamcinolone acetonide; HA, hydroxyapatite nanoparticles; GL, polyethylene glycol ether.

Table 5 Optimum conditions for the burst release reduction

Parameter	Level description	Level	Contribution
A) TR% (w/w)	15	3	1.230
B) Nano HA% (w/w)	1	1	0.041
C) GL% (w/w)	3	2	0.108
Total contribution from all parameters: 1.380
Current grand average of performance: 2.662
Expected result at optimum condition: 1.283

Abbreviations: TR, triamcinolone acetonide; HA, hydroxyapatite nanoparticles; GL, polyethylene glycol ether.

Figure 6 Cumulative TR release kinetics in poly(d,l-lactide-co-glycolide)-hydroxyapatite in phosphate buffer (after 1.5 days).

Figure 7 Effects of variables vs parameter levels.

Figure 8 Effects on pH of triamcinolone acetonide (5%) with PLGA or PLGA-HA.

Abbreviations: PGLA, poly(d,l-lactide-co-glycolide); PGLA-HA, poly(d,l-lactide-co-glycolide) with hydroxyapatite.

Figure 9 SEM image of membranes after immersion in phosphate buffer for 20 days: A) poly(d,l-lactide-co-glycolide) and B) PGLA-HA: poly(d,l-lactide-co-glycolide) with hydroxyapatite.

Figure 10 Diffractograms of A) triamcinolone acetonide B) PLGA and triamcinolone acetonide (15%), C) PLGA and triamcinolone acetonide (15%) and polyethylene glycol ether (3%).

Abbreviation: PLGA, poly(D,L-lactide-co-glycolide).

Figure 11 Scanning electron microgram of poly(d,l-lactide-co-glycolide) membranes: A) 3% and B) 0% polyethylene glycol ether.

Figure 12 Fourier transform near infrared spectra of poly(d,l-lactide-co-glycolide) membranes in the presence of A) 0%, B) 1%, and C) 3% polyethylene glycol ether.

Figure 13 Hot-plate response of mice (n = 5) administered triamcinolone acetonide.

Figure 14 Hot-plate response of mice (n = 5) administered triamcinolone acetonide with poly(d,l-lactide-co-glycolide).