Multicomponent crystals for complexed medical implants mediated foreign body response

Though biomedical implants have revolutionized modern medicine and long-term therapies, their potential is significantly limited by foreign body reaction (FBR). During this immune response, many biomedical implants stimulate a fibrosis reaction, which leads to the implant encapsulation and isolation from the physiological microenvironment, impairing the implant efficiency and even causing its failure. Thus, in order to overcome the host response to the implant it is common to systemically administer anti-inflammatory drugs. This administration lacks the localized effect, causing adverse side effects and the weakening of the immune system, hence posing the patient in risk. Therefore, targeting the implanted area with anti-inflammatory drugs is with great interest^1,2.

Most of the localized therapies are carrier-based systems. The carriers are limited with drug loading capacity, so the formed system is mainly composed of the encapsulation materials rather than the drug itself. Also, common drug delivery vehicles such as polymers have been reported to provoke immune responses. Another issue is the difficulty to control the release profile. A carrier-free crystalline-based system holds the potential to overcome these issues, being promising approach: crystalline formulation creates an administration platform for local treatment, that is 100% composed of the drug, without the need of carriers or stabilizers. Second, studies proved that the release profile of crystals can be prolonged up to years and easy to maneuver, enabling a slow and continuous release profile. Finally, crystals are known for their organized and well packed structure. This gives them enhanced chemical and physiological stability property, which makes them an easy product to store with prolonged shelf-life^1,2.

In this work, we developed a multicomponent crystalline formulation of broad-spectrum anti-inflammatory drugs using varied techniques. This innovative method suggests a combined and localized effect for post-implantation treatment. We examined the multi-component crystal`s designing key parameters, stability under accelerated conditions and studied release under physiological condition. Crystals were fully characterized using varied methods for studying structure and drug molecules distribution along the crystalline lattice using SXRD, PXRD and SEM-EDS. Analysis indicated that the multicomponent crystals are stable and controllable, therefore they are a promising approach for slow-multi drug release treatment applications.

References:

[1] N. Kutner et al., Adv. Funct. Mater. 2021, 2010929, 1.

[2] S. Farah et al., Nat. Mater. 2019, 18, 892.