RESEARCH ARTICLES CURRENT SCIENCE, VOL. 121, NO. 6, 25 SEPTEMBER 2021 775 *For correspondence. (e-mail: wareet@nu.ac.th) Fibroin-coated poly(ethylenimine)-docusate nanoparticles as a novel drug delivery system Duy Toan Pham 1 and Waree Tiyaboonchai 2,3, * 1 Department of Chemistry, College of Natural Sciences, Can Tho University, Can Tho 900000, Vietnam 2 Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, 99 Moo 9, Amphoe Muang, Phitsanulok 65000, Thailand 3 Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, The Center of Excellence for Innovation in Chemistry (PERCH-CIC), Mahidol University, Salaya 73170, Thailand Poly(ethylenimine) (PEI), a polymer with monomers composed of amine groups bound to ethylene mole- cules, has gained increasing interest as a material for nanoparticulate drug delivery systems. However, its high toxicity due to excessive positive charge hinders the versatility of PEI in biomedical applications. Thus, this work aimed to develop and characterize novel PEI-based nanoparticles as a drug delivery system, with reduced surface charge, through polyelectrolyte complexation with a negatively charged compound. Among three candidates, fibroin, sodium docusate (DO) and alginate, DO yielded the best results. Further coating the PEI–DO nanoparticles with fibroin signifi- cantly reduced the system surface charge from +57.3 to +39.3 mV. The fibroin-coated PEI–DO nanopar- ticles were loaded with the model drug α-mangostin, which had a spherical shape with a hydrodynamic size of 260 nm, surface charge of +39.3 mV, entrapment ef- ficiency of 94.6%, and drug loading capacity of 2.96%. The system increased the α-mangostin solubility up to 25 times and showed a fast drug released characteristic within 30 min. Finally, the developed nanoparticles sig- nificantly reduced the α-mangostin hematotoxicity. In conclusion, the novel fibroin-coated PEI–DO nanopar- ticles could be further studied as a potential drug deli- very system. Keywords: Drug delivery system, fibroin, nanoparticles, poly(ethylenimine), sodium docusate, α-mangostin. RECENTLY, research on nanoparticles and their applica- tions, especially in the biomedical field, has gained favourable attention. Due to their unique characteristics, including high surface-area-to-volume ratio, altered quan- tum features and the ability to encapsulate/adsorb various kinds of molecules, nanoparticles have been extensively utilized as drug delivery systems in disease prevention, diagnosis and treatment 1,2 . Nanomedicine could be cate- gorized into three different types; polymer-based, lipid- based and inorganic nanoparticles. Among them, research is mainly focused on polymeric nanoparticles because of their simplicity in preparation, inexpensive and abundant materials and structure modifiability 3 . One of the interesting materials is poly(ethylenimine) (PEI), a polymer with monomers composed of amine groups bound to ethylene molecules. As a water-soluble polycationic substance, PEI and its modified moieties could form non-covalent polyelectrolyte nano-complexes with negatively charged DNA/RNA, and are widely used biologically in cell culture and DNA transfection 4,5 . Moreover, PEI-based nanoparticles have been used as a drug delivery system, carrying doxorubicin (for cancer) 6 , Punica granatum peel extract (for oral infection) 7 and in- sulin (for diabetes) 8 . Nevertheless, PEI-based nanoparticles commonly possess unfavourable side effects of cellular toxicity due to their destabilization or disruption effect on the plasma membranes 4 , possibly caused by the high positive surface charge 9 . Since limited approaches have been explored to decrease its positive charge density, research on PEI to re- duce its toxicity is necessary. Techniques based on chemi- cal modifications such as acetylation, carboxyalkylation, conjugation and PEGylation could alter the PEI structure and affect its transfection ability 9 . Therefore, polyelectro- lyte complexation of PEI with other negatively charged molecules could be a beneficial approach due to its ease of manufacture and up-scaling, simple equipment, environ- ment-friendly nature (i.e. no organic solvents) and versati- lity. To the best of our knowledge, this technique was reported with only dextran sulphate as a negatively charged molecule 7,8,10 . Hence, further studies are necessary. The present study aimed to find the most suitable can- didate to form polyelectrolyte nano-complex with PEI, to reduce its surface positive charge density and preserve its ability to carry drugs. To this end, various (poly)anionic compounds were selected for screening, including silk fibroin, sodium docusate (DO) and sodium alginate. Fibroin is a natural negatively charged protein extracted from Bombyx mori silkworm that has been utilized for numerous biomedical applications 11–14 . DO, a mild laxa- tive and stool softener, is a negatively charged molecule used clinically to treat constipation. Alginic acid, a negatively charged polysaccharide found in the cell walls