Radiolabeling and targeting of lipidic nanocapsules for applications in radioimmunotherapy.
AIM: Radioimmunotherapy is limited in some cases by the low radioactive doses delivered to tumor cells by antibodies or pretargeted haptens. In order to increase this dose, lipidic nanocapsules (LNC) with a hydrophobic core are proposed as radionuclide vectors that could be targeted to cancer cells by a bispecific anti-tumor x anti-hapten antibody after incorporation of different haptens in the nanocapsule membrane. METHODS: To bind different radionuclides to the nanocapsules, several bifunctional chelating agents (BCA) were used to form stable complexes with the radionuclides. Some of them are hydrophilic for LNC shell while others are lipophilic to radiolabel the core. Poly(ethylene glycols) (PEG) were used to increase the residence time in blood. Since PEG can modify haptens recognition by the bispecific antibody and radiolabeling efficiency, haptens, BCA or Bolton-Hunter reagent (BH) were attached to the PEG extremity to optimize accessibility. Specific constructs (DSPE-PEG-haptens, DSPE-PEG-BCA, and DSPE-PEG-BH) were synthesized to develop these new radiolabeled vector formulations. Large amounts of PEG have been introduced by a postinsertion method without important change in nanocapsule size and properties. The nanocapsule core was radiolabeled with a lipophilic [(99m)Tc]SSS complex. RESULTS: Serum stability studies showed that this (99m)Tc-labeling method was efficient for at least 20 h. Concerning the nanocapsule surface, several methods have been performed for (111)In-labeling by using DSPE-PEG-DTPA and for (125)I-labeling with DSPE-PEG-BH. CONCLUSIONS: The nanocapsules labeling feasibility with a variety of radionuclides and their stability were demonstrated in this paper. (+info)
Release of doxorubicin from unstabilized and stabilized micelles under the action of ultrasound.
Polymeric micelles are being investigated as chemotherapy drug delivery carriers using ultrasound as a trigger mechanism. The aim of this paper is to measure the release of Doxorubicin (Dox) from the core of unstabilized Pluronic P105 micelles, Pluronic P105 micelles stabilized with an interpenetrating network of N,N-diethylacrylamide, and micelles of poly(ethylene oxide)-b-poly (N-isopropylacrylamide)-b-poly(oligolactylmethacrylate) with stabilized cores. An ultrasonic exposure chamber with fluorescence detection was used to measure the release of the antineoplastic agent from both stabilized and unstabilized micelles. The release of Dox at 37 degrees C from unstabilized Pluronic appears to be several times higher than release from the more stabilized and crosslinked copolymers at the same temperature. Although there is a difference in the amount of release between the different compounds, the onset of release occurs at about the same ultrasonic power density for all carriers investigated in this study. The threshold of drug release for all the compounds correlates to the emergence of subharmonic peaks detected in the acoustic spectra. We hypothesize that shearing events caused by cavitating bubbles play an important role in the acoustically activated release of chemotherapy agents delivered from various polymeric drug delivery vehicles. (+info)
Efficacy of an MPC-BMA co-polymer as a nanotransporter for paclitaxel.
BACKGROUND: Paclitaxel (PTX) is administered as a solution in polyoxyethylated castor oil (CO) due to its low water solubility, but solvent-induced side-effects may be severe. MATERIALS AND METHODS: PMB30W is a co-polymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and butyl methacrylate (BMA). Cytotoxicities of PTX in PMB30W (PTX-PMB30W) were examined in cell culture and in vivo. RESULTS: PTX-PMB30W and PTX in dimethyl sulfoxide showed similar toxicity in breast cancer cell lines MCF-7, SK-BR-3 and MX-1. Antitumor efficacies of PTX-PMB30W and PTX in CO (PTX-CO) were similar following weekly intraperitoneal administration of 50 mg/kg PTX in nude mice transplanted with MX-1 cells. At 200 mg/kg PTX, all animals died within 1 minute of PTX-CO administration. However, all animals receiving PTX-PBM30W survived. Ulceration occurred following subcutaneous injection of PTX-CO, but injection of PTX-PMB30W did not cause skin changes. CONCLUSION: Our data suggest that PMB30W can act as an effective PTX nanotransporter. (+info)
Production of bionanocapsules in immobilized insect cell culture using porous biomass support particles.
L particles, composed of the L protein of the hepatitis B virus surface antigen, are candidates for a specific gene and drug delivery system. We previously constructed stably transfected insect cells for L particle production. In this study, the cells were successfully immobilized within porous biomass support particles (BSPs) in shake-flask culture. The immobilized cells showed a high specific productivity, comparable to the maximum productivities in static and shake-flask cultures of nonimmobilized cells. (+info)
Efficient preparation of liposomes encapsulating food materials using lecithins by a mechanochemical method.
In order to evaluate to the feasibility of using lecithins for nanocapsules including functional food materials, liposomes were prepared from different commercially available lecithins (SLP-WHITE, SLP-PC70 and PL30S) by the Bangham method, and their physicochemical properties were examined by using a confocal laser scanning microscopy (CLSM) and the measurements of trapping efficiency. There was little difference in the trapping efficiency among the three types of liposomes. In all cases, the trapping efficiency clearly increased with an increase of the lecithin concentration up to 10 wt % , and the maximum efficiency reached at approximately 15%. CLSM observation showed the particle size of liposomes prepared from SLP-WHITE is significantly smaller than that prepared from other lecithins. In addition, liposomal solution prepared from SLP-WHITE remained well dispersed for at least 30 days, while two other liposomal solutions showed a phase separation due to aggregation and/or fusion of liposomes. These results indicated that SLP-WHITE is the most appropriate for the preparation of stable liposomes with well dispersed among the lecithins tested. SLP-WHITE liposomes were then prepared by the mechanochemical method using a homogenizer and microfluidizer, aiming at improving the preparation efficiency and liposome stability. The particle size of the prepared SLP-WHITE liposomes decreased with increasing inlet pressure and the number of processed cycles, and reached between 73 and 123 nm based on the measurement using dynamic light scattering. Moreover, freeze-fracture transmission electron microscopy revealed that the prepared liposomes are small unilamellar vesicles (SUV) with a diameter of approximately 100 nm. The extract of Curcuma longa Linn. (Ukon), which contains curcumins as a functional food material, was then subjected to the mechanochemical method with SLP-WHITE to give liposomes including the functional materials. Interestingly, the trapping efficiency of the liposomes for curcumins was found to reach over 85%. From these results, the present mechanochemical method is very likely to allow us to efficiently prepare stable and functional liposomes from the low-cost lecithin. The method may thus have a potential for manufacturing practical nanocapsules, which serves as a novel carrier of functional food materials. (+info)
In vitro self-assembly of tailorable nanotubes from a simple protein building block.