Glucocorticoids are the cornerstone in the clinic for treatment of
hematological malignancies, including
multiple myeloma. Nevertheless, poor pharmacokinetic properties of
glucocorticoids require high and frequent dosing with the off-target adverse effects defining the maximum dose. Recently, nanomedicine formulations of
glucocorticoids have been developed that improve the pharmacokinetic profile, limit adverse effects and improve solid
tumor accumulation.
Multiple myeloma is a
hematological malignancy characterized by uncontrolled growth of plasma cells. These
tumors initiate increased angiogenesis and microvessel density in the bone marrow, which might be exploited using nanomedicines, such as
liposomes. Nano-sized particles can accumulate as a result of the increased vascular leakiness at the bone marrow
tumor lesions. Pre-clinical screening of novel anti-myeloma
therapeutics in vivo requires a suitable animal model that represents key features of the disease. In this study, we show that fluorescently labeled long circulating
liposomes were found in plasma up to 24 h after injection in an advanced human-mouse hybrid model of
multiple myeloma. Besides the organs involved in clearance,
liposomes were also found to accumulate in
tumor bearing human-bone scaffolds. The therapeutic efficacy of liposomal
dexamethasone phosphate was evaluated in this model showing strong
tumor growth inhibition while free drug being ineffective at an equivalent dose (4 mg/kg) regimen. The liposomal formulation slightly reduced total
body weight of myeloma-bearing mice during the course of treatment, which appeared reversible when treatment was stopped. Liposomal
dexamethasone could be further developed as monotherapy or could fit in with existing
therapy regimens to improve therapeutic outcomes for
multiple myeloma.