Non-ionic thiolated cyclodextrins — the next generation

Abstract

IntroductionThe current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery.Materials and methodsThiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated β-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate.ResultsThiolated β-CDs namely β-CD-SH600 and β-CD-SH1200 displayed 558.66 ± 78 and 1,163.45 ± 96 µmol thiol groups per gram of polymer, respectively. Stability constant (Kc) of 190 M-1 confirmed the inclusion complex formation of miconazole nitrate with β-CD-SH. Inclusion complexes of β-CD-SH600 and β-CD-SH1200 resulted in 157- and 257-fold increased solubility of miconazole nitrate, respectively. In addition, more than 80% of thiol groups were stable even after 6 hours at pH 5. Both β-CD-SH compounds showed at least 1.3-fold improved solubility in water. In contrast to cationic thiolated CDs of the first generation, both thiomers showed no significant cytotoxicity. The mucoadhesive properties of the new thiolated CDs were 39.73- and 46.37-fold improved, respectively.ConclusionThese results indicate that β-CD-SH might provide a new favorable tool for delivery of poorly soluble drugs providing a prolonged residence time on mucosal surfaces.

Thiolated hydroxypropyl-β-cyclodextrin as mucoadhesive excipient for oral delivery of budesonide in liquid paediatric formulation

“…These thiolated polymers, also known as thiomers, are able to form disulphide bonds with cysteine-rich glycoproteins of mucus and have been successfully used to prepare suitable MDDS (Perez-Vilar and Hill, 1999;Bernkop-Schnürch and Steininger, 2000) including thiolated glycogen and glycol-chitosan mucoadhesive polymers (Denora et al, 2016;. Recently, also oligosaccharides such as thiolated cyclodextrin have been developed as a new platform of mucoadhesive excipients suitable for the preparation of oral drug formulations (Moghadam et al, 2018;Asim et al, 2018;Ijaz et al, 2015). Considering all the above mentioned and the evidence that BUD/HP-β-CD inclusion complex showed a reduction of the neutrophil-induced inflammation in a COPD mouse model (dos Santos et al, 1859), the aim of this study was to synthesize a mucoadhesive thiolated HP-β-CD with the capability to form a reversible water soluble inclusion complex with BUD, increasing its permanence on the oesophagus mucosa.…”

Thiol- and Disulfide-Based Stimulus-Responsive Soft Materials and Self-Assembling Systems

“…Thiolation of polymer backbones derived from naturally occurring biopolymers, like hyaluronic acid [ 52 ], chitosan [ 53 , 54 ], alginate [ 55 ], gellan gum [ 56 , 57 ], starch [ 58 ], glycogen [ 59 ], cellulose [ 60 , 61 ], arabinoxylan [ 62 ], xanthan gum [ 63 , 64 ], and cyclodextrins [ 65 , 66 , 67 ] have been studied as mucoadhesive materials. The mucoadhesive properties of thiolated synthetic polymers have been studied, also.…”

Antibacterial and wound healing activities of silver nanoparticles embedded in cellulose compared to other polysaccharides and protein polymers

“…Thiomers with low molecular mass can impart higher permeability and mucoadhesive properties to polymeric formulations (Palazzo et al 2017). For instance, β-CD-SH1200 and β-CD-SH600 illustrated 46.37-and 39.73-fold higher mucoadhesion relative to β-CDs, respectively (Moghadam et al 2018).…”