PubMed · 651953
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B Zinman, M Vranic, A M Albisser, A K Hanna, H L Minuk, E B Marliss. 1978-05-25. Exercise and insulin absorption.. https://doi.org/10.1056/nejm197805252982116
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The objective of this study was to examine the effect of superoxide ion-induced degradation on synthetic absorbable biomaterials. Synthetic absorbable sutures were used as the model compounds. Inflammatory cells, particularly leukocytes and macrophages, are able to produce highly reactive oxygen species, such as superoxide (. O(2)(-)), during inflammatory reactions to foreign materials. Superoxide ions may act as oxygen nucleophile agents to attack biomaterials. In this study, the changes in tensile breaking force, thermal properties, and the surface morphology of five commercial (2/0 in size) synthetic absorbable sutures (Dexon, Vicryl, PDS II, Maxon, and Monocryl) as a function of superoxide ion concentration at 25 degrees C for 24 h were studied. Among the five absorbable sutures and over the concentration range of this study, the monofilament Monocryl suture was the most sensitive toward superoxide ion-induced degradation, followed by Maxon, Vicryl, Dexon, and PDS II sutures. The amount of tensile breaking force loss over a 24 h period ranged from as low as 3% to as high as 80%, depending on the type of absorbable sutures, the reaction time, and the superoxide ion concentration. All five absorbable sutures showed significant reductions in both the T(m) and T(g). Unlike the surface morphological changes of absorbable sutures in conventional buffer solutions, the effect of superoxide ion-induced degradation on the surface morphologies of these five absorbable sutures was unique, particularly the moon-crater-shaped impressions of various sizes and depths found in Monocryl and Maxon sutures, which defied the anisotropic characteristics of fibers.
The role of solvent properties and bath-side composition on the phase inversion dynamics and in vitro protein release kinetics of polylactic-co-glycolic acid (PLGA) solutions has been examined using dark ground imaging, in vitro release rate, and SEM techniques. Thermodynamic phase diagrams for three model systems (PLGA in 1-methyl-2-pyrrolidinone (NMP), triacetin, and ethyl benzoate) suggest two general classes of precipitation behavior, depending on the relative solvent strength and water miscibility. Drug release from the NMP-based system is primarily governed by the dynamics of phase inversion and exhibits a distinct burst region followed by a much slower release. Alternatively, depots with low solvent/water affinity (PLGA in triacetin or ethyl benzoate) undergo much slower phase inversion, resulting in a less porous, more fluid, two-phase structure that also releases protein more uniformly. Addition of a small chain triglyceride or organic salt to the aqueous receptor bath also evokes a significant increase in the mass transfer rate of protein from the low solvent/non-solvent affinity depots. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given.
The purpose of this study was to evaluate the feasibility of intrapulmonary delivery of ABT-431, a selective D1 receptor agonist. Following intratracheal instillation of the drug solution, the lung bioavailability was found to be approximately 75% in dogs. An aerosol suspension formulation was then developed by dispersing the drug in tetrafluoroethane, HFC-134a, with the aid of poloxamer 124 and vitamin E. This ABT-431 MDI aerosol formulation showed about 40% of the particles emitted from the valve and actuator system to be under 5 microm in diameter. Also, the primary package (15 mL aluminum container, DF10/ACT-150 valve, and Micron-4-actuator with the orifice 0.4 mm) was satisfactory for accurate and reproducible dosimetry. Using tracheostomized beagle dogs, the C(max) following tracheal administration of 5 mg aerosolized ABT-431 was found to be 13.3+/-0.9 ng ml(-1) and the AUC(0-24) was estimated at 33.2+/-10.6 h ng ml(-1). The lung bioavailability of the aerosolized drug was 34% compared to intravenous injection in dogs. In humans, results from a single rising dose study demonstrated that rapid absorption of ABT-431 following oral inhalation administration resulted in a dose-dependent increase in the area under the plasma-time curve at dosage levels between 3.3 and 13.2 mg. There is a possibility of up to 25% absorption of the drug from human lung. Thus, pulmonary bioavailability of ABT-431 is significantly greater than that of oral administration. Also, these findings suggest that small and lipophilic compounds, especially with hepatic first pass effect, may be effectively delivered systemically using oral inhalation aerosols.