Stimuli-responsive biomaterials for drug delivery
Creators: name: Abdelmohsen, Hend
Publisher: name: Lancaster University
Year: 2024

description: Corneal neovascularization is one of the most severe ocular diseases.
 Current therapy is limited to repeated intraocular injections of
 antiangiogenic drugs, associated with significant side effects including
 infection, bleeding and retinal detachment. The work presented herein
 attempts to address these issues through the development of degradable and
 cytocompatible light responsive drug delivery systems. These biomaterials
 facilitate the delivery of therapeutic drugs and nucleic acids, with
 tuneable, on demand qualities, which highlights their potential for
 treating a variety of conditions. The translucency of eyes and advances in
 laser technology in ophthalmology make light-responsive delivery of drugs
 feasible. Importantly, light can be applied in a non-invasive fashion;
 therefore, light-triggered drug delivery systems have great potential for
 clinical application. 
 
 Novel methacrylate-based photo-responsive polymers are reported here,
 demonstrating the ability to process them into spherical nanogels. The
 nanogels comprising an immobilized metformin photocage were shown to
 release a consistent amount of drug with temporal control when stimulated
 with light. These nanogels were optimized to release metformin with
 tailored profiles based on their chemical characteristics. 
 
 In order to explore the potential for co-delivery of different drugs
 independently, synthesis of photocleavable drug cage with bathochromic
 shift was successfully accomplished and incorporated into nanogels. The
 resulted particles were shown to exhibit sequential wavelength dependent
 release profiles of ciprofloxacin and metformin in line with their
 irradiation with infrared light. 
 
 Methacrylate nanogels suffer from compromised degradability due to the
 reduced labile groups in their polymer backbone. Therefore, our approach
 was to modify them via co-polymerization with cyclic ketene acetals via
 ring opening mechanism. The formulated nanogels displayed improved
 degradation potential with enzymatic treatment. This should diminish the
 prospects for inflammatory conditions, thus reducing possible impacts on
 the patient and the healthcare system. 
 
 The prepared nanogels in these studies have been shown to generate
 cytocompatible and degradable polymers that can be processed into drug
 delivery system suitable for triggered release of payloads. These polymers
 demonstrated marked ability to suppress the formation of new blood vessels
 in an in vitro cell model for corneal neovascularization. 
 
 
 This project encompasses novel materials utilising photocleavable units to
 enable stimuli-responsive drug delivery. A range of polymeric nanogels
 have demonstrated the ability to consistently release controlled amounts
 of loaded drugs in response to light triggering, which may enable
 suppression of neovascularization. We anticipate these nanogels will
 perform well in vivo by selecting the site of ocular administration and
 non-invasive irradiation with light and thereby improve patient
 compliance, which will be the subject of future studies.