Novel Drug Delivery Systems Tailored for Improved Administration of Glucocorticoids

Abstract

Glucocorticoids (GC) are one of the most popular and versatile classes of drugs available to treat chronic inflammation and cancer, but side effects and resistance constrain their use. To overcome these hurdles, which are often related to the uniform tissue distribution of free GC and their short half-life in biological fluids, new delivery vehicles have been developed including PEGylated liposomes, polymeric micelles, polymer-drug conjugates, inorganic scaffolds, and hybrid nanoparticles. While each of these nanoformulations has individual drawbacks, they are often superior to free GC in many aspects including therapeutic efficacy when tested in cell culture or animal models. Successful application of nanomedicines has been demonstrated in various models of neuroinflammatory diseases, cancer, rheumatoid arthritis, and several other disorders. Moreover, investigations using human cells and first clinical trials raise the hope that the new delivery vehicles may have the potential to make GC therapies more tolerable, specific and efficient in the future.

Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells

“…However, long-term application may become necessary in patients with refractory disease, and under such circumstances, GC therapy often has to be stopped due to adverse effects and second line therapy imitated. As an alternative, new strategies to prevent side effects of GC are currently being developed including the targeted delivery by nanocarrier systems [ 7 ]. For example, the application of a GC-copolymer conjugate has been found to ameliorate disease symptoms in a mouse model of IBD while preventing the development of osteoporosis [ 8 , 9 ].…”

Development and characterization of polymeric-based nanoparticles for sustained release of amoxicillin – an antimicrobial drug

“…In this context, to achieve a suitable timed-controlled drug release resulting in steady-state plasma concentration over a longtime period, some new and interesting drug delivery systems have been developed which aim at targeting specific cell types or tissues. It has been also proved that many novel carrier systems have improved pharmacokinetic and pharmacodynamic properties of various drug molecules [1,2].…”

Therapeutic Efficacy of Intratendinous Delivery of Dexamethasone Using Porous Microspheres for Amelioration of Inflammation and Tendon Degeneration on Achilles Tendinitis in Rats

“…Glucocorticoid treatment via injection plays a protective role by suppressing inflammation. However, several adverse effects including pain after drug injection, rupture of the Achilles tendon, skin atrophy, and depigmentation are induced by repetitive injections [7,8,16]. For these reasons, we examined whether DEX/ PMSs suppressed inflammatory responses and effectively prevented tendon degeneration in Achilles tendinitis models via the intratendinous treatment of DEX/PMSs.…”

“…However, despite the strong therapeutic effects, their longterm treatments affect tendon healing deleteriously and induce tendon rupture [7,8]. Mikolyzk et al [9] and Torricelli et al [10] suggested that glucocorticoid treatments reduces tendon strength and also inhibits proliferation and collagen synthesis of tenocytes.…”

“…To conquer such drawbacks, drug delivery systems (DDSs) are continuously under development to achieve controlled and/or sustained drug release over a prolonged period of time [11]. DDSs containing liposomes, nanoparticles, 3D scaffolds, and microspheres improve bioavailability and pharmacokinetics [8,11,12]. Liposomes, microspheres, and nanoparticles have been used as injectable scaffolds for noninvasive or minimally surgical applications.…”