Molecular-Gated Drug Delivery Systems Using Light-Triggered Hydrophobic-to-Hydrophilic Switches

Abstract

A photo-responsive molecule-gated drug delivery system (DDS) based on silicone-hydrogel (poly(HEMA-co-PEGMEA)) interpenetrating polymer networks (IPN) functionalized with carboxylated spiropyran (SPCOOH) was designed and demonstrated as an on-demand DDS. The triggered release mechanism relies on controlling the wetting behaviour of the surface by light, exploiting different hydrophobicity between the "closed" and "open" isomers of spiropyran as the photo-switchable molecular gate on the surface of IPN (SP-photogated IPN). The light-triggered release of doxycycline (DOX) as the model drug indicated that the spiropyran (SP) molecules provide a hydrophobic layer around the drug carrier and have a good gate-closing efficiency for IPNs with 20-30 % hydrogel content. Upon UV light irradiation the SP convert to the open hydrophilic merocyanine state, which triggers the release of DOX. These results were compared with a previously developed SP-bulk modified IPN using the same hydrogel as a control, proving the efficiency of the gated IPN system. The covalent attachment of SPCOOH to the alcohol groups of the hydrogel and the structural change caused by UV light was indicated with FTIR analysis. XPS results also confirms the presence of SP by indicating the atomic percentage of nitrogen with respect to the hydrogel content.

Spiropyran-Based Drug Delivery Systems

“…The beneficial properties of IPNs have been exploited to develop stimuli-responsive DDSs. These DDSs leverage the change in interactions between the polymers, loaded drug molecules and solvent on stimuli application, thus enabling highly controlled drug delivery without disruption to the structure of the IPNs ( Ghani et al, 2021a ; 2021b ).…”

“…In an alternative approach, Ghani et al investigated a SP-photogated IPN-based DDS for on-demand delivery ( Ghani et al, 2021b ). The IPN was synthesised as follows: firstly, a silicone elastomer prepared using supercritical CO 2 technology was impregnated with a hydrophilic poly (HEMA- co -PEGMEA) hydrogel.…”

“…These results indicate that the proposed SP-photogated IPN does indeed show promise for on-demand delivery of hydrophilic drugs. However, careful tuning of hydrogel composition is required in order to ensure a compromise is reached between high cumulative drug release and minimal premature release ( Ghani et al, 2021b ).…”

Molecular Switches—Tools for Imparting Control in Drug Delivery Systems

“…Molecular switches offer a non-invasive and bio-compatible mechanism by which encapsulated bioactive compounds can be released at a target site in a responsive and controlled manner when a specific stimulus is applied. Hence, molecular switches can improve the selectivity and efficacy of the administered drug and enhance its biosafety profile ( Raza et al, 2019 ; Ghani et al, 2021 ). The different stimuli that can trigger these molecular switches can generally be divided into endogenous and exogenous stimuli ( Raza et al, 2019 ).…”

Tough complex hydrogels transformed from highly swollen polyelectrolyte hydrogels based on Cu2+ coordination with anti-bacterial properties

“…4 Therefore, antibiotic-free strategies for treating bacterial infections are actively being developed. Biomaterials with different anti-bacterial modes such as silver-based anti-bacterial, 5 photoresponsive anti-bacterial, 6 synergistic effect anti-bacterial, 7 and inherent antibacterial 8 have been widely reported as a potential substitute for antibiotics.…”