Assessment of temperature-sensitive properties of ionically crosslinked sodium alginate/hydroxypropyl cellulose blend microspheres: preparation, characterization, and in vitro release of paracetamol

Today, polymer systems can be formed to respond to single stimuli or multiple stimuli by changing their properties. The use of these systems, which are designed to be sensitive to stimuli, is expanding in a wide range of applications. Herein, microspheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn²⁺ ions. FTIR, DSC, TGA, SEM, and particle size measurements were used to describe the blend microspheres. Low critical solution temperatures (LCST) of polymer blends at different ratios were determined and the biggest change according to the LCST value of HPC was found to be approximately 1-2 °C lower than 41 °C in microspheres with a NaAlg/HPC ratio of 50/50. In vitro release experiments of paracetamol from microspheres were carried out in a gastrointestinal tract simulation environment at two different temperatures (37 °C and 47 °C). From the release profiles, paracetamol release varied depending on the NaAlg/HPC ratio, the paracetamol content in the microspheres, the exposure time to Zn²⁺ ions, and the pH of the medium. Among the microsphere formulations, the highest entrapment efficiency was 57.86%, obtained for B₇ formulation microspheres with a NaAlg/HPC ratio of 70/30, a paracetamol loading percentage of 20%, and a crosslinking time of 5 min.RESEARCH HIGHLIGHTSMicrospheres of sodium alginate (NaAlg) and hydroxypropyl cellulose (HPC) sensitive to dual stimuli for the controlled release of model drug paracetamol were produced by the ionotropic gelation method in the presence of Zn²⁺ ions.LCST values of the microspheres with a NaAlg/HPC ratio of 50/50 were significantly lower by 1-2 °C than the LCST value of HPC, and the release results supported the temperature sensitivity of the microspheres.Among the microsphere formulations, the highest entrapment efficiency was 57.86% obtained for B₇ formulation microspheres.These microspheres can be used as a temperature-sensitive drug delivery system in the biomedical field and also as an encapsulation system of cancer drugs for cancer treatment modalities such as hyperthermia.