Search Results (3)

Messenger RNA (mRNA) therapeutics are redefining treatment approaches in vaccines, cancer immunotherapy, protein replacement, and gene editing. Lipid nanoparticles have enabled early clinical successes, but they can be limited by liver-dominant biodistribution, long-term storage stability, and systemic tolerability. Polymeric delivery systems offer a versatile alternative, with tunable physicochemical properties enabling precise control over mRNA complexation, protection, release, and targeting. This review examines recent progress across polyethyleneimine derivatives, poly(β-amino ester)s, poly(amino acid)s, polyesters, dendrimers, charge-altering releasable transporters, and lipid-polymer hybrids. We highlight strategies such as structural modification, stimuli-responsive designs, and high-throughput polymer screening that enhance stability, reduce cytotoxicity, and enable organ- or cell-specific delivery. Addressing challenges in immunogenicity, biodistribution, and manufacturing scalability will be pivotal to translating these innovations into safe and effective mRNA therapeutics. Full article

Background/Objectives: The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy with consideration of the anatomical and physiological protective barriers of the eye. Interferon alpha has been employed to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This study focuses on the design of an injectable pH-responsive and protective nanoparticle system dispersed into a thermo-responsive hydrogel for site-specific sustained delivery of interferon alpha (IFN-α2b) in the treatment of ocular surface tumours. Methods: The synthesis of a poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer (PECE) was undertaken. The IFN-α2b was encapsulated in poly(β-amino ester) (PBAE) nanoparticles (NP) with pH-responsive characteristics to proposedly release the IFNα-2b in response to the acidic nature of the tumour microenvironment. This was followed by characterisation via Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance (¹H-NMR) analysis, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) analysis, thermogravimetric analysis (TGA), and thermal-transition analysis of the PECE hydrogels. Results: Release studies demonstrated that the PBAE nanoparticulate PEG-PCL-PEG hydrogel was both pH-responsive, while providing controlled release of IFN-α2b, and thermo-responsive. Release analysis highlighted that IFN-α2b-loaded NP dispersed into the hydrogel (IFNH) further prolonged the release of IFN-α2b with a pH-responsive yet controlled release rate in an acidic environment simulating a tumour microenvironment. The developed system proved to be biocompatible with human retinal pigment epithelial cells and the released IFN-α demonstrated bioactivity in the presence of an A172 glioblastoma cell line. Conclusions: In conclusion, the PECE hydrogel has promising potential for application as an ocular drug delivery system for the treatment of ocular tumours and could potentially overcome and prevent the drawbacks associated with the commercially available IFN-α2b injection. Full article

Disulfides are used extensively in reversible cross-linking because of the ease of reduction into click-reactive thiols. However, the free-radical scavenging properties upon reduction are often under-considered. The free thiols produced upon reduction of this disulfide material mimic the cellular reducing chemistry (glutathione) that serves as a buffer against acute oxidative stress. A nanoparticle formulation producing biologically relevant concentrations of thiols may not only provide ample chemical conjugation sites, but potentially be useful against severe acute oxidative stress exposure, such as in targeted radioprotection. In this work, we describe the synthesis and characterization of highly thiolated poly (β-amino ester) (PBAE) nanoparticles formed from the reduction of bulk disulfide cross-linked PBAE hydrogels. Degradation-tunable PBAE hydrogels were initially synthesized containing up to 26 wt % cystamine, which were reduced into soluble thiolated oligomers and formulated into nanoparticles upon single emulsion. These thiolated nanoparticles were size-stable in phosphate buffered saline consisting of up to 11.0 ± 1.1 mM (3.7 ± 0.3 mmol thiol/g, n = 3 M ± SD), which is an antioxidant concentration within the order of magnitude of cellular glutathione (1–10 mM). Full article