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Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.

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Aliphatic polyester biodegradable microspheres have been extensively studied for controlled and minimally invasive in situ protein delivery. However, they are commonly characterized by protein denaturation via acidic polyester degradation products, whereas their supraphysiologic modulus contributes to the inflammatory response upon implantation. To address these limitations, low-melting-point poly(ε-caprolactone-co-glycolide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-glycolide) (PEG-(PCG) 2 ) copolymers were prepared and characterized for their ability to release bioactive stromalderived factor-1α (SDF-1α) as a representative therapeutic protein. The PEG molecular weight was chosen such that it would be crystalline at room temperature to promote easy handling of the microspheres, whereas the molecular weight and composition of the hydrophobic PCG blocks were adjusted to ensure the polymer was a viscous amorphous liquid at 37 °C. Microspheres prepared from the triblock copolymers completely degraded within 8 weeks in vitro with a minor decrease in microenvironmental pH. A prolonged release of SDF-1α was observed with its bioactivity highly retained after encapsulation and release.