Smart Solid Drug Delivery Systems: Exploring the pH Sensitivity of Cashew Gum-Doxorubicin Prodrug

Ribeiro, Irisvan S.; Leonardo, Adisom L. S.; Carneiro, Maria J. M.; Costa Filho, Raimundo N.; Freire, Rosemayre S.; Sousa, Jeanlex S.; Araújo, Gisele S.; Marinho Filho, José D. B.; Araújo, Ana J.; Paula, Haroldo C. B.; Feitosa, Judith P. A.; Paula, Regina C M. de

doi:10.21577/0103-5053.20240087

home Sumário navigate_before Anterior Atual Seguinte navigate_next

home Sumário

Article • J. Braz. Chem. Soc. 35 (11) • 2024 • https://doi.org/10.21577/0103-5053.20240087 linkcopy

Smart Solid Drug Delivery Systems: Exploring the pH Sensitivity of Cashew Gum-Doxorubicin Prodrug

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Polysaccharide-based prodrugs formed via pH-responsive covalent interactions can be used to prepare nanoparticles for drug delivery to tumor cells. This study reports the synthesis of cashew gum-doxorubicin prodrugs via Schiff base (CG-S-DOX) and amide bonds (CG-A-DOX), both of which exhibit pH-responsive behavior. Synthesis was confirmed using spectroscopic techniques. Drug-binding content and efficiency were higher for CG-S-DOX than for CG-A-DOX. The capacity of the nanoparticles to self-organize in aqueous media was confirmed using fluorescence spectroscopy, dynamic light scattering, and atomic force microscopy. Both prodrugs possessed sizes < 200 nm and showed responsive doxorubicin-release profiles in the acidic tumor cell microenvironment. Compared with free DOX, the CG-S-DOX and CG-A-DOX prodrug had significantly reduced cytotoxicity against non-tumor cells (L929). CG-S-DOX, but not CG-A-DOX, showed antitumor activity against HCT-116 (human colorectal cancer) and MCF-7 (human breast cancer) cells. An uptake assay confirmed that the nanoparticles were easily taken up by HCT-116 cells. These results together with the great reduction in cytotoxicity against non-tumor cells, confirm the potential of CG-S-DOX prodrug nanoparticles as a reliable and efficient system for the effective delivery of doxorubicin to tumor cells.

Keywords:
cashew gum; Schiff base; conjugates; cancer; pH responsive

Prodrug	Yield / %	DBC / %	DBE / %	CAC /(µg mL⁻¹)
CG-S-DOX	81 ± 1^a	28 ± 1^a	75 ± 1^a	27 ± 1^a
CG-A-DOX	80 ± 1^a	24 ± 1^b	64 ± 2^b	32 ± 2^b

Sample	DLS			SEM	AFM
Sample	Size^A / nm	PDI	Zeta potential^B / mV	Size / nm	Size / nm
CG-S-DOX	159 ± 11^a	0.29 ± 0.06^a	−18 ± 2^a	74 ± 16^a	ca. 20
CG-A-DOX	193 ± 8^b	0.28 ± 0.03^a	−20 ± 2^a	75 ± 10^a	ca. 62

Nanoparticle	pH	Model parameter
Nanoparticle	pH	k_s / h⁻¹	k_on / 10⁻³ h⁻¹	k_off / h⁻¹	∆G / 10⁻²¹ J	R²
CG-S-DOX	5.0	0.34	3.39	2.59×10⁻³	−1.15	0.980
CG-S-DOX	7.4	0.28	1.29	4.96×10⁻⁴	−4.09	0.990
CG-A-DOX	5.0	0.38	4.58	2.12×10⁻³	−3.29	0.984
CG-A-DOX	7.4	0.41	1.56	6.80×10⁻⁴	−9.82	0.996

Sample	IC₅₀ (SI) / (µg mL⁻¹)
Sample	L929	HCT-116	MCF-7
CG-S-DOX^a	28.20 ± 4.40	1.33 ± 0.25 (21.2)	2.86 ± 1.08 (9.86)
CG-A-DOX^a	> 120	> 60	> 60
OCG	> 250	> 250	> 250
DOX	0.42 ± 0.16	0.12 ± 0.03 (3.5)	0.29 ± 0.08 (1.45)

vertical_align_top show_chart

more_horiz close
- image
- translate
- link
- article
- vertical_align_top
- file_download
- show_chart
- image
- translate
- link
- article

location_on

Sociedade Brasileira de Química Instituto de Química - UNICAMP, Caixa Postal 6154, 13083-970 Campinas SP - Brazil, Tel./FAX.: +55 19 3521-3151 - São Paulo - SP - Brazil
E-mail: office@jbcs.sbq.org.br

rss_feed Acompanhe os números deste periódico no seu leitor de RSS

[TFN1] Data are presented as the mean ± S.D. (n = 3). Statistical analysis was performed using one-way ANOVA, followed by Tukey’s test. Means with the same superscript letters in a column are not significantly different (p > 0.05), whereas those with different letters in the same column are (p < 0.05). DBC: drug-binding capacity; DBE: drug-binding efficiency; CAC: critical aggregation concentration.