Corn Starch Nanoparticles as an Effective and Nontoxic Nanocarrier Involving Histone Deacetylase Inhibitors for Smart Drug Delivery
نویسندگان
1 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
2 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
3 Tashkent State Medical University, Tashkent, Uzbekistan
4 Mamun University, Khorezm, Uzbekistan
5 Samarkand State Medical University, 140100 Samarkand, Uzbekistan
6 Bukhara State Pedagogical Institute, Bukhara, Uzbekistan
7 Samarkand State University named after Sharof Rashidov, University Boulevard, 15, Samarkand, 703004, Uzbekistan
8 Urgench State University, Khorezm, Uzbekistan
9 Samarkand Campus, University of Economics and Pedagogy, Samarkand, Uzbekistan
10 Jizzakh Branch of the National University of Uzbekistan, Jizzakh, Uzbekistan
11 Bukhara State Medical Institute, Uzbekistan
12 Bukhara State Medical Institute named after Abu Ali ibn Sino, Bukhara, Uzbekistan
13 Bukhara State Pedagogical Institute, Bukhara, Uzbekistan;
doi
10.22052/JNS.2025.04.067چکیده
This study presents a nontoxic starch-based nanocarrier platform for epigenetic drug delivery, focusing on histone deacetylase inhibitors (HDACi). We engineered maleate-esterified corn starch nanoparticles (CS-NPs) with a sub-100 nm size (78 ± 9 nm by SEM; favorable renal clearance window) and a carboxylated surface to enable gentle, solvent-disciplined preparation without compromising biocompatibility. The CS-NPs were loaded with vorinostat (SAHA) via non-covalent encapsulation, achieving an actual loading of 9.8 ± 0.3% (theoretical 12%) and an encapsulation efficiency of 82 ± 2%, with minimal burst release (~1.7 ± 0.2% over initial cycles). HDAC inhibition assays using HDAC1 revealed that CS-SAHA retains potency (IC50 = 18 ± 2 nM) essentially indistinguishable from free SAHA (16 ± 1 nM); isoform selectivity across HDAC1/2/6 remained consistent post-encapsulation, indicating preserved pharmacological profiling. Comprehensive physicochemical characterization showed a predominantly amorphous, covalently grafted matrix with robust thermal stability (TGA up to ~250 °C) and surface carboxylate groups, supporting stability during sterilization and storage. In vitro trafficking data demonstrate enhanced uptake in CD44-overexpressing cells, while hematological parameters in vivo suggest low acute toxicity. Collectively, these CS-NPs exemplify a scalable, GRAS-compatible, biodegraded platform capable of delivering hydrophobic HDAC inhibitors with preserved activity and favorable safety margins, outlining a translational path toward starch-based epigenetic depots and IND-ready protocols. Future work will address in vivo epigenetic proof-of-concept, real-time imaging, and expansion to other HDACi classes and targeting ligands.
