Vol.:(0123456789) 1 3 Chemical Papers https://doi.org/10.1007/s11696-019-01024-0 ORIGINAL PAPER Investigating the efect of freezing temperature and cross‑linking on modulating drug release from chitosan scafolds Eshwari Dathathri 1  · Goutam Thakur 1  · K. B. Koteshwara 2  · N. V. Anil Kumar 3  · Fiona Concy Rodrigues 1 Received: 8 June 2019 / Accepted: 4 December 2019 © Institute of Chemistry, Slovak Academy of Sciences 2019 Abstract The aim of this study was to investigate the efect of altering design variables like cross-linking and freezing temperature (at a time) on morphology of freeze-dried chitosan scafolds and modulation of release of Diclofenac sodium (model drug). Freeze-dried chitosan scafolds produced at − 80 °C, cross-linked with genipin, showed swelling of 163.52 ± 9.95% with sustained drug release of 26.37 ± 10.47% over 24 h (P < 0.05). In comparison, uncross-linked scafolds produced at − 80 °C showed higher swelling of 173.58 ± 8.23% and drug release of 28.67 ± 2.40% (P < 0.05). Uncross-linked scafolds produced using freezing temperature of − 20 °C also showed higher swelling of 228.77 ± 9.84% and release of 30.58 ± 3.25% (P < 0.05). Release kinetics followed Higuchi model with Fickian difusion, thereby indicating a swelling-dependent release. Altering the design parameters also showed signifcant changes in pore size and porosity, thereby supporting the swelling and drug delivery behavior from scafolds. Keywords Chitosan scafolds · Genipin · Freezing temperature · Sustained drug release Introduction Advanced drug delivery systems have gained importance in the recent years as they impose some advantages over the conventional drug delivery systems such as site-specifc administration of drugs, lowering toxicity and enhanced therapeutic beneft (Ahmed 2015; Zhang et al. 2013; Mody 2016; Rufato et al. 2018). Besides, the drugs can be released at a controlled rate to optimize pharmacokinetics and phar- macodynamics behavior of drugs (Mody 2010; Vogelson 2001; Wattanutchariya and Changkowchai 2014, Li et al. 2018). Modern drug delivery systems in the form of pol- ymer-based matrices have gained popularity due to their unique properties of biocompatibility and biodegradabil- ity, enabling better therapeutic efect and improved release kinetics (Vogelson 2001; James et al. 2014). Hydrogels, films, scaffolds are some of the polymer-based carriers adopted in modern drug delivery systems, showing immense potential as controlled drug delivery matrices (James et al. 2014; Campos et al. 2009; Garg et al. 2013; Narayanaswamy and Torchilin 2019). Both synthetic and natural polymers have been employed to design advanced drug delivery matrices. Chitosan, a natu- ral polymer which is nontoxic, exhibits excellent antibacte- rial and hemostatic properties making it a good candidate for wound healing and tissue engineering applications (Riva et al. 2011; Giri et al. 2012; Ali and Ahmed 2018). Additionally, it is exploited in hydrogels and scafolds for developing various drug delivery carriers (Garg et al. 2012a). The current trend shows an extensive use of chitosan freeze-dried scafolds for the regeneration of tissues, as these scafolds exhibit excel- lent biocompatibility, improved stability, high porosity and interconnectivity (O’Brien 2011; Thakur and Rousseau 2016; Dhandayuthapani et al. 2011; Ikeda et al. 2014). Chitosan is mostly dissolved in acetic acid; however, a number of studies have reported in which lactic acid was utilized to dissolve chi- tosan instead of acetic acid, as acetic acid emanates an undesir- able pungent smell, reduces sensorial quality and produces a * Goutam Thakur goutam.thakur@manipal.edu 1 Department of Biomedical Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India 2 Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India 3 Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India