Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery

Abstract

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.

Chiral nanocrystals grown from MoS2 nanosheets enable photothermally modulated enantioselective release of antimicrobial drugs

“…In comparison to (R)-DNCs-2, (S)-DNCs-2 had a much stronger interaction energy with levofloxacin, which generated efficient antimicrobial effects. This finding contributed to establishment of a controllable and sustained release formulation 51 – 55 .…”

Facile Preparation of β-Cyclodextrin-grafted Chitosan Electrospun Nanofibrous Scaffolds as a Hydrophobic Drug Delivery Vehicle for Tissue Engineering Applications

“…To verify this, we used DEX, as it is a lipophilic substance, 32 and synthetic glucocorticoid, as it is used clinically as an anti-inflammatory drug. 33 First, we quantified the drug loading amount on CTS and βCTS ENs. We confirmed that the βCTS ENs successfully loaded a larger amount of DEX compared to the bare CTS ENs, indicating a 2.3-fold increase in loading (data not shown).…”

“…As mentioned above, we anticipated that β-CD-grafted CTS ENs may have hydrophobic drug loading capacity. To verify this, we used DEX, as it is a lipophilic substance, and synthetic glucocorticoid, as it is used clinically as an anti-inflammatory drug . First, we quantified the drug loading amount on CTS and βCTS ENs.…”

Embolic microspheres for transarterial chemo-embolization (TACE) featuring inherent radiopacity and carrying crystalline drugs at their surface, in dimples or inside major cavities

“…In non-human primates and in rodents, the foreign body response was substantially delayed (for 6 and 15 months, respectively). Taken together, the data on dexamethasone dimer (Battiston et al 2021), GW2580 Farah et al 2019, paclitaxel , rapamycin (Farah et al 2013) and triamcinolone (Gursharan et al 2021) point out that crystalline drugs combine a high drug density with slow topical delivery through dissolution. Dissolution appears to occur at the surface of the crystals and thus obeys zero-order kinetics, i.e., initial-burst release (which is often encountered with bio-absorbable polymer coatings) can thus be avoided.…”