Polypseudorotaxanes of Pluronic® F127 with Combinations of α- and β-Cyclodextrins for Topical Formulation of Acyclovir

Abstract

Acyclovir (ACV) is one of the most used antiviral drugs for the treatment of herpes simplex virus infections and other relevant mucosal infections caused by viruses. Nevertheless, the low water solubility of ACV limits both its bioavailability and antiviral performance. The combination of block copolymer micelles and cyclodextrins (CDs) may result in polypseudorotaxanes with tunable drug solubilizing and gelling properties. However, the simultaneous addition of various CDs has barely been investigated yet. The aim of this work was to design and characterize ternary combinations of Pluronic® F127 (PF127), αCD and βCD in terms of polypseudorotaxane formation, rheological behavior, and ACV solubilization ability and controlled release. The formation of polypseudorotaxanes between PF127 and the CDs was confirmed by FT-IR spectroscopy, X-ray diffraction, and NMR spectroscopy. The effects of αCD/βCD concentration range (0–7% w/w) on copolymer (6.5% w/w) gel features were evaluated at 20 and 37 °C by rheological studies, resulting in changes of the copolymer gelling properties. PF127 with αCD/βCD improved the solubilization of ACV, maintaining the biocompatibility (hen’s egg test on the chorio-allantoic membrane). In addition, the gels were able to sustain acyclovir delivery. The formulation prepared with similar proportions of αCD and βCD provided a slower and more constant release. The results obtained suggest that the combination of Pluronic with αCD/βCD mixtures can be a valuable approach to tune the rheological features and drug release profiles from these supramolecular gels.

Host‐Fueled Transient Supramolecular Hydrogels

“…Therefore, as an ideal drug carrier, F127 has been approved in medical applications and widely used that way [22] . Above the critical micelle concentration, F127 can self‐assemble to form spherical micelles with PEO shells and PPO cores in aqueous solutions [23] . When the chemical fuel (α‐CD) is added to the solution containing F127 and α‐amylase, the PEO chain of F127 can penetrate the cavity of α‐CD, and thus a white gel based on host–guest interactions can form.…”

“…[22] Above the critical micelle concentration, F127 can self-assemble to form spherical micelles with PEO shells and PPO cores in aqueous solutions. [23] When the chemical fuel (α-CD) is added to the solution containing F127 and α-amylase, the PEO chain of F127 can penetrate the cavity of α-CD, and thus a white gel based on host-guest interactions can form. At the same time, α-amylase-regulated hydrolysis of α-CD destroys the host-guest inclusions, leading to the collapse of the hydrogel networks.…”

Cyclodextrins in the antiviral therapy

“…CD-based polymers, either the CD-polymers, nanosponges, or CDcombinations with other polymers, can play an increasing role in topical applications, particularly in the mucosal and transdermal administrations [54,[56][57][58]. The controlled release of acyclovir in ocular and subcutaneous administrations from a (hydroxy)propyl methylcellulose/cellulose acetate phthalate sandwiched acyclovir-βCD complex was successful [49], but the composition is still far from an everyday application.…”

Inclusion complexes of triblock L35 copolymer and hydroxyl propyl cyclodextrins: a physico-chemical study

“…30 Pluronics can be included inside the cyclodextrins generating polypseudorotaxanes with peculiar structures and thermo-responsive properties. As examples, Pluronic F127 included inside both α-CD and β-CD induced the formation of complexes with excellent delivery characteristics towards the antiviral acyclovir, 31 whereas fine periodic structures were achieved by the self-assembly of Pluronic F108 and β-CD. 32 Complexes based on γ-CD and PNIPAAM diblock copolymers exhibited thermo-responsive behaviour as evidenced by their investigation at the solid/liquid interface.…”