Misrepresentation of treatments for arthritis.
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Sixty-nine patients or parents of patients were interviewed during a five-week period. Each interviewee was given a questionnaire listing commonly recommended unproved drugs, diets, and miscellaneous treatments, and was instructed to respond to each remedy as follows: Have you tried it? Have you considered trying it? Has it been recommended by someone else? Six patients (8.7%) had tried at least one unproved remedy, four (5.8%) considered trying some other remedy, and recommendations to seek other remedies had been made to 17 patients (24.6%). Laetrile and assistance from faith healers were the remedies named most frequently.
The evidence for the claims that laetrile (amygdalin) can prevent or control cancers has been reviewed. The beta-glucosidase content of cancer tissues is low compared to that of normal liver and small intestine. Cancer tissues contain the enzyme rhodanese in amounts comparable to that of liver and kidney and hence, cannot be attacked selectively by cyanide release through beta-glucosidase action on amygdalin. Amygdalin does not have the properties of a vitamin. Rats have been reared for several generations on diets devoid of cyanogenic glycosides, without developing neoplasms. Experiments with tumor-bearing rodents have demonstrated no curative properties by amygdalin administration. Amygdalin is not as non-toxic as claimed, particularly when ingested orally, and especially when taken with plant material high in beta-glucosidase. The claims for cure and control of cancers in humans have been refuted by distinguished physicians who specialize in the treatment of cancer patients. The writings of laetrile proponents are filled with erroneous and absurd statements. The propaganda for the doctrine of "freedom of choice in cancer treatment" deludes many individuals with treatable cancer to reject proven methods of treatment.
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PURPOSE: This study was performed to develop a reliable aqueous size-exclusion chromatography (SEC) method to obtain the absolute molar masses and distributions of various cationic polymers used in gene delivery. METHODS: Water-soluble cationic [2-(dimethylamino) ethyl methacrylate] polymers (PDEs) with different molar masses and low polydispersities were synthesized by living polymerization and these were used to optimize the SEC conditions. Online coupled multiangle light scattering (MALS) detection was applied to obtain the absolute molar masses. Narrow fractions of high molar mass were obtained by semipreparative SEC. RESULTS: It was found that 0.3 M NaAc (pH 4.4) is a suitable eluent in combination with Shodex OHpak SB columns for SEC analysis of PDEs and other cationic polymers, such as poly(L-lysine) and poly(ethylene imine). The absolute molar masses of different PDEs were determined directly using SEC-MALS. A calibration curve was established using narrow PDEs. CONCLUSIONS: A reliable routine method for molar-mass characterization of cationic polymers was established. Because standards of known molar masses with narrow distributions are not commercially available for most polymers used in pharmaceutics and biotechnology, the procedure described in this work can also be applied for molar-mass characterization of other water-soluble polymers.
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Polymeric micelles are emerging as attractive drug delivery systems. Hydrophobic drugs including photosensitizers for photodynamic therapy can be covalently bound or physically entrapped in the core of the micelles and thus be systemically delivered to, for example, tumors using passive or active targeting strategies. Polymers used for photosensitizer encapsulation include pluronics, poly(ethylene glycol) (PEG)-lipid conjugates, and pH-sensitive poly(N-isopropylacrylamide) based micelles or polyion complex (PIC) micelles. This paper reviews the results obtained so far, including drug loading, biodistribution studies, and therapeutic efficiency. The pH-sensitive micelles appear to be promising candidates for photosensitizer delivery.
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Block copolymers of poly(ethylene glycol) (PEG) as a hydrophilic block and N-isopropylacrylamide (PNIPAAm) or poly (NIPAAm-co-N-(2-hydroxypropyl) methacrylamide-dilactate) (poly(NIPAAm-co-HPMAm-dilactate)) as a thermosensitive block, are able to self-assemble in water into nanoparticles above the cloud point (CP) of the thermosensitive block. The influence of processing and the formulation parameters on the size of the nanoparticles was studied using dynamic light scattering. PNIPAAm-b-PEG 2000 polymers were not suitable for the formation of small and stable particles. Block copolymers with PEG 5000 and 10000 formed relatively small and stable particles in aqueous solutions at temperatures above the CP of the thermosensitive block. Their size decreased with increasing molecular weight of the thermosensitive block, decreasing polymer concentration and using water instead of phosphate buffered saline as solvent. Extrusion and ultrasonication were inefficient methods to size down the polymeric nanoparticles. The heating rate of the polymer solutions was a dominant factor for the size of the nanoparticles. When an aqueous polymer solution was slowly heated through the CP, rather large particles (> or = 200 nm) were formed. Regardless the polymer composition, small nanoparticles (50-70 nm) with a narrow size distribution were formed, when a small volume of an aqueous polymer solution below the CP was added to a large volume of heated water. In this way the thermosensitive block copolymers rapidly pass their CP ('heat shock' procedure), resulting in small and stable nanoparticles.
This paper presents a novel self-gelling hydrogel potentially suitable for controlled drug delivery and tissue engineering. The macroscopic gels are obtained by mixing dispersions of oppositely charged crosslinked dextran microspheres. These microspheres in turn were prepared by crosslinking of dextran derivatized with hydroxyethyl methacrylate emulsified in an aqueous poly(ethylene glycol) solution. Negatively or positively charged microspheres were obtained by addition of methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA) to the polymerization mixture. Rheological analysis showed that instantaneous gelation occurred when equal volumes of oppositely charged microspheres, dispersed in buffer solutions of pH 7, were mixed. The shear modulus of the networks could be tailored from 30 to 6500 Pa by varying the water content of the system. Moreover, controlled strain and creep experiments showed that the formed networks were mainly elastic. Importantly for application of these systems, e.g. as controlled matrix of pharmaceutically active proteins, it was demonstrated that the hydrogel system has a reversible yield point, meaning that above a certain applied stress, the system starts to flow, whereas when the stress is removed, gel formation occurred. Further it was shown that the network structure could be broken by either a low pH or a high ionic strength of the medium. This demonstrates that the networks, formed at pH 7 and at low ionic strength, are held together by ionic interactions between the oppositely charged dextran microspheres. This system holds promise as injectable gels that are suitable for drug delivery and tissue engineering applications.
In this study, the in vivo biocompatibility of physically crosslinked dextran hydrogels was investigated. These hydrogels were obtained by mixing aqueous solutions of dextran grafted with L-lactic acid oligomers and dextran grafted with D-lactic acid oligomers. Gelation occurs due to stereocomplex formation of the lactic acid oligomers of opposite chirality. Since gelation takes some time, in situ gel formation is possible with this system. A number of sterilization methods was evaluated for their effect on the chemical and physical properties of the hydrogel. It was shown that of the investigated options (filtration, gamma irradiation, dry-heat and autoclaving) dry-heat sterilization was the preferred method to prepare sterile gels suitable for in vivo evaluations. Two types of stereocomplex gels were prepared and implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 30 days. A mild ongoing foreign body reaction was observed characterized by infiltration of macrophages. Giant cells were only scarcely formed and the low numbers of lymphocytes showed that priming of the immune system is hardly involved. Importantly, the gels fully degraded in vivo within 15 days, which is in good agreement with the in vitro degradation behaviour of these gels. In conclusion, stereocomplexed dextran-oligolactic gels showed good biocompatibility which makes them suitable candidates for the design of controlled release devices for pharmaceutically active proteins.