Chemically Cross-Linked Poly(β-Cyclodextrin) Particles as Promising Drug Delivery Materials

Abstract

One-pot synthesis of poly­(β-cyclodextrin) (p­(β-CD)) micro-/nanoparticles was accomplished using two different cross-linkers, divinyl sulfone (DVS) as p­(β-CD)-1 and trimethylolpropane glycidyl ether (TMPGDE) as p­(β-CD)-2. High gravimetric yields of 84 ± 4 and 62 ± 6%, respectively, were attained for p­(β-CD)-1 and p­(β-CD)-2 particles. The p­(β-CD)-1 and p­(β-CD)-2 particles had spherical shapes with 5.09 ± 0.24 and 0.60 ± 0.01 μm diameters, respectively, and exhibited good water dispersibility at physiological pH, and their isoelectric points were calculated correspondingly to be pH 1.1 and 1.2. The surface areas of p­(β-CD)-1 and p­(β-CD)-2 particles were determined to be 4.76 ± 0.6 and 2.18 ± 0.2 m2/g, respectively. Moreover, p­(β-CD) particles were found to be biocompatible with more than 98% cell viability on human retinal pigment epithelial (ARPE-19) cells at 0.1 mg/mL concentration. Also, p­(β-CD)-1 particles exhibited 52.81 ± 9.5% Fe­(II) chelation capacity at 1.0 mg/mL concentration. The hemolysis and coagulation tests revealed that p­(β-CD)-1 particles possessed excellent blood compatibility with a 1.18 ± 0.60% hemolysis ratio and a 92.02 ± 1.02% clotting index even at 2.0 mg/mL concentration, whereas the safety limit of p­(β-CD)-2 particles for blood interactions was determined to be 0.5 mg/mL. The in vitro drug release performances of p­(β-CD)-1 and p­(β-CD)-2 particles for hydrophobic acyclovir and hydrophilic vancomycin model drugs at pH 7.4 PBS showed sustained releases of 2.14 ± 0.34 and 1.34 ± 0.43 mg/g acyclovir and 51.90 ± 1.09 and 61.26 ± 3.71 mg/g vancomycin within 24 h, respectively. Kinetic modeling of experimental release data revealed the best fit for drug release from p­(β-CD) particles mediated by the Korsmeyer–Peppas model.

Orally Administered, Biodegradable and Biocompatible Hydroxypropyl–β–Cyclodextrin Grafted Poly(methacrylic acid) Hydrogel for pH Sensitive Sustained Anticancer Drug Delivery

“…The surface morphology of prepared hydrogel was studied by SEM using an optical microscope (Vega 3, Tuscan). An optimum sized sample was placed on an aluminum stump coated with a thin layer of gold (~3000 Å) and photomicrographs were collected [ 37 ].…”

Role of Cyclodextrin Cross-Linker Type on Steroid Hormone Micropollutant Removal from Water Using Composite Nanofiber Membrane

“…However, the absorbance ratio ( A 1079 / A 1023 ) of βCD-TPTE slightly decreased to 0.45. This decrease can be attributed to the peaks overlapping with the C–O–C stretching, which are associated with the formation of ether groups after cross-linking. , …”

“…Despite the widespread use of EP for βCD cross-linking, its toxicity and carcinogenicity have been documented, , rendering it unsuitable for water treatment applications. Consequently, alternative and more biocompatible cross-linkers have been reported in the literature for βCD cross-linking. − Triphenylolmethane triglycidyl ether (TMTE) and trimethylolpropane triglycidyl ether (TPTE) have been selected in this study as alternative cross-linkers based on characteristics of lower toxicity, commercial availability, and similar epoxy groups suitable for cross-linking reactions, as present in EP. − TMTE and TPTE have been reported as cross-linkers in biomaterials including dental materials − and drug delivery materials. , Chung et al reported TMTE cross-linked photocurable material that aimed to be applied in dental applications showing low curing shrinkage, low water sorption, and low water solubility. Suner et al reported the biomaterials containing TPTE, which showed fast enzymatic degradation of 80–90% using pectinase and amyloglucosidase.…”

Green Synthesis of Polycyclodextrin/Drug Inclusion Complex Nanofibrous Hydrogels: pH-Dependent Release of Acyclovir

“…40 Even in one of the related studies reported by Demirci et al, the cross-linked CD particles of acyclovir were formed to provide a sustained release with respectable blood compatibility. 41 In our previous study, the polymer-free CD-IC nanofibers of acyclovir were successfully produced using highly water-soluble hydroxypropyl-β-cyclodextrin (HPβCD) for the purpose of fastdisintegrating oral delivery systems. 42 The potential of acyclovirincorporated polymeric nanofibers has also been reported for HSV-2 treatments 43 and ocular 44 and topical delivery 45 using PLGA, PCL, and polyvinylpyrrolidone (PVP) polymers.…”

“…The administration dosage form of acyclovir includes tablets, cream, ointment, injection, and eye drops. , However, the therapeutic potential of acyclovir is diminished because of its limited water solubility, low bioavailability, and low membrane permeability. , On the other hand, there has been a notable effort to improve the therapeutic efficiency of this drug by improving its poor physicochemical properties using different approaches such as microemulsions, hydrogels, liposomes, nanoparticles, and CDs . Even in one of the related studies reported by Demirci et al, the cross-linked CD particles of acyclovir were formed to provide a sustained release with respectable blood compatibility …”