Title : An injectable CarboCell depot technology for local, sustained dual-antibiotic delivery in bone infections
Abstract:
Chronic bone infections remain difficult to treat, as systemic antibiotic therapy often fails to achieve sufficient local drug concentrations in poorly vascularized, infected bone while simultaneously exposing patients to systemic toxicity risk. Carbohydrate-derived lipophilic materials are emerging as versatile injectable depot systems for this challenge, owing to their chemical tunability, hydrophobicity-driven release control, and compatibility with diverse payloads. Here we present CarboCell, an injectable, viscosity-tunable depot platform engineered for sustained local delivery of antibiotics and other new chemical entities (NCEs). The CarboCell matrix, a proprietary blend of carbohydrate esters, triglycerides, and solvent, undergoes in situ phase transition upon contact with aqueous tissue fluids, forming a stable depot that supports high loading and controlled release of both lipophilic and amphiphilic drugs. We report its formulation, physicochemical characterization, and dual-antibiotic efficacy in vitro and in vivo, in mouse and porcine bone-infection models. CarboCell was formulated from customized carbohydrate esters (SuBen, 70% w/w), triglyceride (GTO, 15% w/w), and ethanol (15% w/w); adjusting esterification level, triglyceride ratio, and solvent fraction tuned viscosity across a range spanning low-viscosity injectable liquids to semi-solid depots. Compatibility with diverse NCEs, including modified antibiotics and oligonucleotides, was assessed, and a dual-antibiotic system (gentamicin and clindamycin) was used to evaluate co-loading and co-release behaviour. Viscosity was measured by rotational viscometry; following subcutaneous injection in mice, residual depots were collected over time and drug content quantified by HPLC. Dual-antibiotic CarboCell depots were further evaluated in porcine intraosseous and soft-tissue models, using microdialysis and tissue extraction, to characterize local versus systemic antibiotic exposure over time. CarboCell formed a stable in situ depot upon contact with tissue fluids, supporting localized retention and distribution of therapeutics, while maintaining an injectable viscosity of 2500 cps at 25°C. In subcutaneous mice, depots provided sustained, multi-week release of encapsulated antibiotics. In porcine intraosseous models, CarboCell formed a well-defined local depot and enabled high, sustained antibiotic levels in both bone (up to 75% release within one week) and surrounding soft tissue (60% gentamicin, 50% clindamycin release), while systemic plasma antibiotic levels remained minimal throughout the study period, confirming targeted local delivery with markedly reduced systemic exposure relative to conventional systemic dosing. Together, these results demonstrate that CarboCell is a tunable, injectable carbohydrate-ester depot technology capable of sustained, localized dual-antibiotic delivery to bone and soft tissue, achieving high local drug exposure while minimizing systemic antibiotic burden. As a biodegradable, needle-injectable system requiring no surgical implantation or removal, CarboCell offers a translationally attractive platform for treating orthopaedic and bone infections. Its compatibility with diverse payload classes, including oligonucleotides and other NCEs, further positions CarboCell as a broadly applicable local-delivery platform, with potential extension beyond infection to other indications requiring sustained, tunable local release of therapeutic payloads.
Conclusions:
▪ CarboCell forms a stable in-situ depot upon contact with tissue fluids, supporting localized retention and distribution of therapeutics.
▪ CarboCell maintains injectable viscosities (2500 cps at 25 °C) while providing sustained, multi‑week release of encapsulated antibiotics in s.c mice, in vivo.
▪ CarboCell forms a defined intraosseous depot in vivo and enables high, sustained local antibiotic levels in both bone (up to 75% release within a week) and surrounding soft tissue (60% genta, 50% clinda).
▪ CarboCell achieves high local antibiotic exposure in bone and tissue while maintaining minimal systemic levels, confirming targeted local delivery and reduced systemic burden.
