Preparation and characterization of carrageenan/ halloysite nanotube nanocomposite films for potential transdermal drug delivery application

The attention of using synthetic polymers in medical and pharmaceutical purposes has been drawn towards polysaccharide-based materials due to their inertness, non-toxicity, biocompatibility, biodegradability, low cost and abundant availability. Among polysaccharides, there has been very little work on carrageenan (CRG) as a candidate for transdermal drug delivery patches. Carrageenan is a sulphated polysaccharide with simple gelation mechanism, thermo-reversible ability and tunable viscoelastic properties. Despite its interesting properties and potential, CRG has low mechanical strength and possesses fast drug release rate which lead to fast disintegration of polymer matrix. In this study, a CRG film was prepared by solution casting with the addition of halloysite nanotube (HNT) as reinforcing filler. Significant mechanical improvement of CRG film was achieved at 3 pph loading of HNT with increased tensile strength and elongation at break, and decreasing modulus; optimum strength of 8.54 MPa, elongation percentage of 53.72% and modulus of 13.76 MPa. The CRG/HNT film with 3 pph HNT also showed high swelling capacity (~97%) with longer disintegration time of more than 20 minutes. The morphological observations and Fourier transform infrared (FTIR) spectra confirmed that good dispersion and interactions were achieved between CRG and HNT. The nanocomposite film has better moisture repellent and thermal stability compared to the pure CRG film. The X-ray diffraction (XRD) of the nanocomposite film revealed preferential orientation of the HNT in CRG matrix and increase in the level of crystallinity. The loading of diclofenac sodium (DS) and benzalkonium chloride (BKC) to the HNT separately showed that the position of drug in the HNT was charge dependent. The DS was found to entrap inside the HNT lumen and has better sustainable release than the BKC which deposited mostly onto the external surface of HNT. The Franz diffusion study revealed that the inclusion of HNT minimized the burst effect of both drug models, sustained the release of DS by ~23% after 12 hours and prolonged the complete release of BKC for more than 7 hours. The nanocomposite film with DS possessed a flux (J) of 0.0117 mg/cm2/h and a permeability coefficient (P) of 5.91 x 10-3 cm/h, while the film patch with BKC possessed a J value of 0.0489 mg/cm2/h and a P value of 24.7 x 10-3 cm/h. The release of DS from the patches follows first order kinetic model while the BKC follows zero order kinetic model. The cytotoxicity study indicated improved patch biocompatibility by the HNT addition and the drugs loading induced certain toxicity towards the film patches. Based on these results, the addition of HNT has improved the performance of CRG film as a matrix patch. Therefore, the CRG/HNT film presents potential and feasibility as a material for transdermal drug delivery system