BACKGROUND & AIMS: Osteotropic drug-delivery systems have been proposed as a means to provide drugs with affinity to bone tissues. Drugs or proteins have been linked chemically to bone-seeking agents, such as bisphosphonates (BPs); alternatively, drug-loaded nanoparticles have been used to target specific tissues, such as tumor areas. In our current research, these approaches were merged by synthesizing a novel bone-seeking polymer conjugate, from which targetable nanoparticles can be produced. MATERIALS & METHODS: An amino-BP, alendronate (ALE) was bound covalently to a biodegradable polymer, poly(lactic-co-glycolide) (PLGA), containing a free end carboxylic group. Blood compatibility and cytotoxicity were assessed in vitro. RESULTS & DISCUSSION: By a classical solvent-evaporation method, nanoparticles with a mean size of 200-300 nm were prepared from the conjugate; sterilization was achieved by gamma-irradiation, confirming their potential as injectable drug nanocarriers. Owing to the presence of the BP residue, PLGA-ALE nanoparticles were adsorbed onto hydroxyapatite to a higher extent than pure PLGA nanoparticles. The PLGA-ALE conjugate did not induce either hemolysis or alterations of the plasmatic phase of coagulation, or cytotoxic effects on endothelial cells and trabecular osteoblasts. CONCLUSION: The prepared conjugate represents a novel biomaterial that is able to provide nanoparticles, which can be further loaded with drugs, such as anticancer agents, and addressed to osteolytic or other bone diseases.
BACKGROUND & AIMS: Osteotropic drug-delivery systems have been proposed as a means to provide drugs with affinity to bone tissues. Drugs or proteins have been linked chemically to bone-seeking agents, such as bisphosphonates (BPs); alternatively, drug-loaded nanoparticles have been used to target specific tissues, such as tumor areas. In our current research, these approaches were merged by synthesizing a novel bone-seeking polymer conjugate, from which targetable nanoparticles can be produced. MATERIALS & METHODS: An amino-BP, alendronate (ALE) was bound covalently to a biodegradable polymer, poly(lactic-co-glycolide) (PLGA), containing a free end carboxylic group. Blood compatibility and cytotoxicity were assessed in vitro. RESULTS & DISCUSSION: By a classical solvent-evaporation method, nanoparticles with a mean size of 200-300 nm were prepared from the conjugate; sterilization was achieved by gamma-irradiation, confirming their potential as injectable drug nanocarriers. Owing to the presence of the BP residue, PLGA-ALE nanoparticles were adsorbed onto hydroxyapatite to a higher extent than pure PLGA nanoparticles. The PLGA-ALE conjugate did not induce either hemolysis or alterations of the plasmatic phase of coagulation, or cytotoxic effects on endothelial cells and trabecular osteoblasts. CONCLUSION: The prepared conjugate represents a novel biomaterial that is able to provide nanoparticles, which can be further loaded with drugs, such as anticancer agents, and addressed to osteolytic or other bone diseases.
Authors: Juan Pablo Cattalini; Aldo R Boccaccini; Silvia Lucangioli; Viviana Mouriño Journal: Tissue Eng Part B Rev Date: 2012-05-14 Impact factor: 6.389
Authors: Qian Yin; Li Tang; Kaimin Cai; Rong Tong; Rachel Sternberg; Xujuan Yang; Lawrence W Dobrucki; Luke B Borst; Debra Kamstock; Ziyuan Song; William G Helferich; Jianjun Cheng; Timothy M Fan Journal: Proc Natl Acad Sci U S A Date: 2016-07-25 Impact factor: 11.205