Optimization and synthesis of etoricoxib-loaded low molecular weight chitosan nanoparticles

Arfan, Aulia Rhamdani; Ilmiawati, Auliya; Sugita, Purwantiningsih

doi:10.1590/0103-8478cr20210656

Acessibilidade / Reportar erro

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

BIOLOGY • Cienc. Rural 52 (11) • 2022 • https://doi.org/10.1590/0103-8478cr20210656 copy

Optimization and synthesis of etoricoxib-loaded low molecular weight chitosan nanoparticles

Otimização e síntese de nanopartículas de quitosana de baixo peso molecular carregadas com etoricoxib

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT:

This study reports the optimization of the preparation of etoricoxib (ETX)-loaded low molecular weight of chitosan (LMWC) nanoparticles (ETX-LMWC-NPs) by ionic gelation method with sodium tripolyphosphate (TPP) as cross-linking agent. The independent variables (LMWC/TPP mass ratio, LMWC, and poloxamer 188 concentration) were formulated and optimized using response surface methodology (RSM) Box-Behnken design (BBD) with three levels for each factor. Size of particles, polydispersity index (PDI), and encapsulation efficiency was investigated as the dependent variable. ETX-LMWC-NPs were characterized by particle size analyzer, scanning electron microscope, UV-Vis spectrophotometry, and Fourier transforms infrared spectroscopy. The ETX-LMWC-NPs have an average particle size of 259.91 nm, a PDI of 0.041, and encapsulation efficiency of 51.25%. ETX-LMWC-NPs are spherical and have a spectrum at wavenumber 1656 cm^-1 and 718 cm^-1, respectively, indicating the presence of C=N and C-Cl originating from the ETX compound. The ETX release profile at pH 1.2 and 6.8 mediums approach the Korsmeyer-Peppas model. ETX released pH 1.2 did not differ significantly from free ETX with a maximum 10-12% release. ETX release at pH 6.8 had a maximum release of 21% and showed a 19% increase in dissolution rate than free ETX. The ETX-LMWC-CSNPs prepared by optimum formula (2.65 % LMWC, 5.5 LMWC/TPP mass ratio, and 1 mg/mL) showed stable monodispersity nanoparticles and easily soluble in water.

Key words:
chitosan; ntoricoxib; nanoparticle; poloxamer 188

Universidade Federal de Santa Maria Universidade Federal de Santa Maria, Centro de Ciências Rurais , 97105-900 Santa Maria RS Brazil , Tel.: +55 55 3220-8698 , Fax: +55 55 3220-8695 - Santa Maria - RS - Brazil
E-mail: cienciarural@mail.ufsm.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] E-mail: purwantiningsih@apps.ipb.ac.id. ^*Corresponding author.

LMWC/TPP mass ratio	Mean particle size (nm)	PDI	Encapsulation efficiency (%)
2.5	287.00	0.100	39.0924
3.5	229.74	0.050	49.8595
4.5	178.86	0.009	35.1007
5.5	148.13	0.041	44.2786
6.5	183.10	0.093	51.1720

LMWC (%)	Mean particle size (nm)	PDI	Encapsulation efficiency (%)
2.5	178.86	0.0090	35.1007
3.0	199.93	0.1810	38.1867
3.5	410.09	0.0280	43.7046

Poloxamer 188 (mg/mL)	Mean particle size (nm)	PDI	Encapsulation efficiency (%)
0	796.25	0.041	42.7695
1	178.86	0.009	35.1007
1.5	281.20	0.003	53.1665
2.0	391.66	0.040	59.3297

Formula	--------------------Variable independent-------------------			-------------------------------Response---------------------------------
Formula	A	B	C	Y₁	Y₂	Y₃
1	3.5	5.5	1.5	353.27	0.052	37.4339 ± 1.04
2	2.5	4.5	1.0	178.86	0.009	38.9580 ± 1.42
3	2.5	3.5	1.5	332.49	0.022	35.7875 ± 1.88
4	3.5	3.5	1.5	373.37	0.023	39.3540 ± 2.94
5	3.0	4.5	1.5	322.75	0.076	45.2794 ± 1.33
6	3.0	5.5	2.0	294.5	0.085	50.1155 ± 0.07
7	3.5	4.5	2.0	354.92	0.025	47.2417 ± 1.45
8	3.0	3.5	2.0	335.71	0.160	42.3080 ± 2.06
9	2.5	5.5	1.5	318.11	0.144	46.1379 ±1.15
10	3.0	4.5	1.5	328.22	0.080	43.9520 ± 0.68
11	2.5	4.5	2.0	391.66	0.040	38.3663 ± 0.33
12	3.0	5.5	1.0	270.67	0.090	45.4543 ± 1.45
13	3.5	4.5	1.0	410.09	0.028	43.6202 ± 0.12
14	3.0	4.5	1.5	432.33	0.829	49.1477 ± 2.88
15	3.0	3.5	1.0	414.63	0.036	40.6088 ± 0.92

Response	--------------------------------------------------Optimum formula----------------------------------------------------
Response	Prediction	Observation	95 % CI low	95 % CI high	95 % PI low	95 % PI high
Mean particle size (nm)	259.203	259.91	88.34	319.78	128.035	390.371
PDI	0.113	0.040	0.0008	0.225	-0.336	0.562
Encapsulation efficiency (%)	47.2311	51.252	43.5860	51.4994	41.4938	52.9684

Drug release kinetics model	ETX-LMWC-NPs in pH 1.2	ETX-LMWC-NPs in pH 6.8
Zero order Q = kt	$y = 0.045 x + 4.4105$ R² = 0.7068	$y = 0.0079 x + 14.609$ R² = 0.0826
First order ${\ln [A]}_{t} = {\ln [A]}_{0} - kt$	$y = - 5 x 10^{- 4} x - 0.4566$ R² = 0.7147	$y = - 9 x 10^{- 5} x - 0.5708$ R² = 0.0776
Higuchi $Q = {kt}^{1 / 2}$	$y = 0.8388 x + 0.5211$ R² = 0.8346	$y = 0.2966 x + 12.232$ R² = 0.1962
Hixson-Crowell $Q_{0}^{1 / 3} - Q_{t}^{1 / 3} = kt$	$y = - 1 x 10^{- 4} x + 0.8588$ R² = 0.7121	$y = - 2 x 10^{- 5} x + 0.8269$ R² = 0.0793
Korsmeyer-Peppas Q = ktⁿ	$y = 0.6545 x - 0.3399$ R² = 0.8373	$y = 0.1924 x - 0.7795$ R² = 0.4322