ทศพล นิจอนันต์. Development of polystyrene based cationic exchange nanofibers for drug delivery. Doctoral Degree(Pharmaceutical Technology). Central Library of Silpakorn University. : , 2013.
Development of polystyrene based cationic exchange nanofibers for drug delivery
Abstract:
In this study, cationic exchange nanofibers were prepared from polystyrene (PS) and
poly(styrene sulfonic acid-co-maleic acid)/polyvinyl alcohol (PSSA-MA/PVA) using electrospinning,
crosslinking and/or sulfonation. Electrospinning parameters i.e. PS concentration, solvent ratio, salt in solvent,
inner diameter of tip and PSSA-MA/PVA ratios, crosslinking parameters i.e. sulfuric acid/formaldehyde ratios,
the percentage of silver sulfate, crosslinking time and temperature, and/or sulfonation parameters i.e. time and
temperature were optimized. The geometrical, chemical, and mechanical properties of the nanofiber ion
exchangers were characterized. The remaining fibers, ion exchange capacity (IEC), water content, and
cytotoxicity were evaluated. Cationic drugs namely dextromethorphan hydrobromide (DXM), propranolol
hydrochloride (PPL), chlorpheniramine maleate, diphenhydramine hydrochloride (DPH), and salbutamol
sulphate (SAL) were loaded in polystyrene nanofiber ion exchangers (PSNIE) for oral delivery, whereas
neomycin sulphate was loaded in PSSA-MA nanofiber ion exchangers for topical use. Loading capacity, drug
release, release kinetic, antibacterial activity and stability were investigated. PSNIE were successfully
prepared using electrospinning, crosslinking with sulfuric acid/formaldehyde and sulfonation in sulfuric acid.
The morphology and diameter of PS fibers depended on PS concentration, the properties of solvents and %
tetrabutyl ammonium bromide (TBAB). The smallest diameter and the narrowest diameter distribution of PS
fibers (376 ± 36 nm) were obtained from 15% w/v PS solution in dimethylacetamide (DMAc) with 0.025% w/v
TBAB. The degree of crosslinking depended on the sulfuric acid/formaldehyde ratio and crosslinking time.
The PS fibers with the highest degree of crosslinking were obtained at a sulfuric acid/formaldehyde ratio of
95/5 and after 75 min of crosslinking. The presence of silver sulfate, sulfonation time, and temperature
affected the ion exchange capacity (IEC). The PS fibers crosslinked with a sulfuric acid/formaldehyde ratio of
90/10 for 10 min and sulfonated at 100oC for 30 min showed a maximum IEC of 3.21 meq/g-dry-PSNIE.
PSSA-MA/PVA nanofiber ion exchangers were successfully prepared using electrospinning and crosslinking
with thermal treatment. Smooth fibers without beads were obtained from PSSA-MA/PVA mixed in ratios up to
0.4/1. The degree of crosslinking increased with an increase of crosslinking time and temperature, which
significantly affected IEC. The temperature and time for successful crosslinking were 120oC (5-7 h) and 130-
140oC (17 h). The cationic drugs were successfully loaded in PSNIE and PSSA-MA/PVA nanofiber ion
exchangers. DXM provided the highest loading in PSNIE while DPH gave the highest percentage release in
both simulated gastric and intestinal fluid (SGF and SIF). The release kinetics of all drugs in SGF and SIF
showed the best fit with the particle diffusion model. Neomycin could be loaded in the PSSA-MA/PVA
nanofiber ion exchangers. The loading capacity was increased upon increasing the neomycin concentration.
An initial concentration of 0.1% w/v neomycin showed the highest loading capacity (65.7 mg/g-dry fibers). The
neomycin-loaded nanofiber ion exchangers demonstrated satisfactory antibacterial activity against both Grampositive
and Gram-negative bacteria and were stable during storage at 25oC for 6 month. In conclusion, both
PSNIE and PSSA-MA/PVA nanofiber ion exchangers have the potential to use as drug carrier in novel delivery
system for oral and topical application.