Surface‐modified poly(lactide‐co‐glycolide) nanospheres for targeted bone imaging with enhanced labeling and delivery of radioisotope

Abstract

Surface-modified nanospheres can be utilized for targeting drugs and diagnostic agents to the bone and bone marrow while extending their circulation time in the blood stream. The surface modification of poly(lactide-co-glycolide) (PLGA) nanospheres by radioisotope carrying poly(ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblock copolymers (Poloxamer 407) has been assessed by in vitro characterization and in vivo biodistribution studies after intravenous administration of the nanospheres to the mouse. A hydroxyphenylpropionic acid, a ligand for 125 I and 131 I labeling, was conjugated to the hydroxyl group of the Poloxamer 407 by using dicyclohexyl carbodiimide. The ligand-conjugated Poloxamer 407 was adsorbed onto the surface of PLGA nanospheres. Surface coating was confirmed by measuring both size distribution and the surface charge of the nanospheres. Besides, 125 I-labeling efficiency, radiolabeling stability, whole body imaging, and biodistri-bution of the radioisotope-labeled nanospheres were examined. Ligand-labeled, surface-modified PLGA nanospheres were in 100-nm size ranges, which may be adequate for long-circulation and further bone imaging. 125 I-labeling efficiency was Ͼ90% and was more stable at human serum for 24 h. A noticeable decrease in liver or spleen uptake was obtained by the surface-modified nanospheres. 125 I-labeled nanospheres showed higher blood maintenance and bone uptake compared with stannous colloid with the same size distribution. Therefore, a fully biodegradable, radioisotopecarrying, surface-modified nanosphere system has been developed as a promising tool for targeting bone and bone marrows.

Poly(lactic-co-glycolic acid) Nanoparticles as Delivery Systems for the Improved Administration of Radiotherapeutic Anticancer Agents

“…A wide variety of targeted delivery strategies are currently being explored, and the use of nanotechnology is now playing a more significant role in the development of novel delivery systems . NPs are particularly attractive platforms for drug delivery considering that (i) they can be composed of a plethora of different organic and inorganic compounds, (ii) they can be designed with a mechanism that allows them to store and subsequently release a “payload” in response to a specific stimulus, and (iii) they can be functionalized with various chemical moieties to enable the targeting of tumor tissue or to make them biocompatible. ,− Polymer NPs composed of poly­(lactic- co -glycolic acid) (PLGA) have become a popular component in various drug-delivery systems because they degrade over time in the presence of water and exhibit high biocompatibility and their surface can be readily functionalized. − Multiple PLGA NP delivery systems are capable of encapsulating and releasing various organic compounds, ,, but thus far, attempts to encapsulate radionuclides or radiotherapeutic agents have been limited. − In this letter, we report the synthesis and characterization of PLGA NPs encapsulating a variety of metal ions including Ba, Gd, and Ce, which act as surrogates of α-emitting radionuclides based on their similar chemical characteristics (Table S-1). Using surrogate cations minimizes the handling of radioactive materials and avoids the generation of radioactive waste throughout the development and testing processes of these delivery systems.…”

Improving the blood clearance time of 125I labeled Dex-g-PMAGGCONHTyr by copolymerization

“…For blood tissue at 1 h after intravenous injection, the mean organ uptake of 125 I labeled Dexg-PMAGGCONHTyr is 0.97%ID/g, and the mean organ uptake of the 125 I labeled Dex-g-P(MPEG-co-MAGGCONHTyr), Dex-g-PMAGGCONHPEG 3k -NHTyr and Dex-g-P(HPMA-co-MAGGCONHTyr) are 1.22, 1.30, 7.22%ID g À1 , respectively. Although PEGylated dextran copolymers have the effect of biological inert and can be slow down the rapid recognition by the reticuloendothelial system, [7][8][9][10][11][12] it is obvious that blood percentage of PEGylated dextran copolymers in present work is only slightly higher than that of Dex-g-PMAGGCONHTyr. This may be due to the molecular weight of PEG on blood tissue distribution.…”

“…Among many carriers that were investigated, the presence of poly(ethylene glycol) (PEG) or poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) were found to prolong the blood clearance time of the carriers. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] PEGylated copolymers can prolong the blood clearance time, which is due to that the presence of PEG can reduce the rapid recognition of the carriers by the reticuloendothelial system. [7][8][9][10][11][12] HPMA based copolymer can prolong blood clearance time and increase tumor concentration, which suggest that HPMA based copolymer drug delivery systems are attractive tools for more effectively treating various forms of advanced solid malignancy.…”

“…[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] PEGylated copolymers can prolong the blood clearance time, which is due to that the presence of PEG can reduce the rapid recognition of the carriers by the reticuloendothelial system. [7][8][9][10][11][12] HPMA based copolymer can prolong blood clearance time and increase tumor concentration, which suggest that HPMA based copolymer drug delivery systems are attractive tools for more effectively treating various forms of advanced solid malignancy. 6,[13][14][15][16][17][18][19][20] Moreover, macromolecular carriers with PEG or PHPMA parts are mainly determined by the molecular weight and the physicochemical properties of the polymer.…”

“…In order to improve the blood clearance time of Dex-g-PMAGGCONHTyr copolymers, the structure and components of the copolymers are needed to be redesigned. On the consideration of the advantages of PEG or PHPMA components on the biodistribution and blood clearance time, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] PEG or PHPMA can be introduced into the Dex-g-PMAGGCONHTyr copolymers. Therefore, new dextran graft copolymers, including dextran graft poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-P(HPMA-co-MAGGCONHTyr)), dextran graft poly(methacrylpolyethylene glycol-co-N-methacryloylglycylglycine)-tyrosine conjugates (Dex-g-P(MPEG-co-MAGG-CONHTyr)), and dextran graft poly(N-methacryloylglycylglycine) copolymers conjugated with O-(2-aminoethyl) polyethylene glycol (M n ¼ 3000 g mol À1 ) and tyrosine (Dex-g-PMAGGCONH-PEG 3k -NHTyr) were designed and synthesized.…”