The surface characteristics of intravenously administered particulate drug carriers decisively influence the protein adsorption that is regarded as a key factor for the in vivo fate of the carriers. Latex nanoparticles were synthesized to study the influence of different basic and acidic functional groups on particulate surfaces on the protein adsorption from human serum. The protein mass adsorbed to the particles was assessed by BCA protein assay, the protein adsorption patterns were analyzed by two-dimensional electrophoresis. Considerable differences in the protein adsorption with regard to preferential adsorbed proteins were detectable for the different functional groups. Possible correlations between the surface characteristics and the protein adsorption are shown and discussed. The knowledge concerning the interactions of proteins and nanoparticles can be used for a rational development of particulate drug carriers and can also be useful for an optimized design of medical devices, e.g., hemodialysis membranes or implants.
The objective of the present study was to incorporate the hydrophilic drug diminazenediaceturate at a high loading into lipid nanoparticles by creating nanoparticles from lipid-drug conjugates (LDC). IR and DSC data showed that the antitrypanosomal drug diminazene is able to react with fatty acids to form water-insoluble salts like diminazenedistearate and -dioleate. The salts could be transformed into nanoparticles using high-pressure homogenization technique, established for solid lipid nanoparticles (SLN). By using polysorbate 80 as surfactant, physically stable LDC nanoparticle dispersions of both salts could be obtained. The mean PCS diameters and polydispersity indices were 364 nm and 0.233 for diminazenedistearate and 442 nm and 0.268 for diminazenedioleate, respectively. Due to the composition of the LDC bulk materials, nanoparticles with a high drug load of 33% (w/w) were obtained even for this highly water-soluble drug diminazenediaceturate. The new carrier system of LDC nanoparticles overcomes one limitation of SLN, i.e. the limited loading capacity for hydrophilic drugs. Transforming water-soluble hydrophilic drugs into LDC and formation of nanoparticles allows prolonged drug release and targeting to specific sites by i.v. injection. These results provide a first basis of using LDC-polysorbate 80 nanoparticles for brain delivery of diminazene to treat second stage human African trypanosomiasis (HAT).
Our study shows that BALF contains inhibitory components for non-viral gene transfer. We could not detect a specific inhibitory component, but inhibition was most likely due to the change in the surface charge of the gene vectors. Interestingly, there is evidence for complement activation when the route of pulmonary gene vector administration is chosen. Consequently, shielding of gene vectors to circumvent interaction with the ASL environment should be a focus for pulmonary administration in the future.
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