Adriamycin-loaded bovine albumin microspheres have been prepared by a technique that allows preparation and administration to animals on the same day. Criteria adopted for injection were that microspheres should be stable and of a size such as to become trapped in capillary beds. These conditions were fulfilled by preparing microspheres using glutaraldehyde concentrations greater than 0.5 per cent and the appropriate combination of stirring speed and continuous phase viscosity. After systemic administration rats were sacrificed at intervals and major visceral organs examined for entrapped microspheres and serum for released drug. Microspheres sieved out in the first capillary bed encountered, the lung, then following biodegradation they disappeared at a rate dependent on the amount of cross-linking agent used in their preparation. In contrast to bolus injection, serum drug levels after microsphere administration indicated an initial rapid release followed by a more protracted phase lasting at least 24 h. This latter observation is consistent with drug release during biodegradation of carrier.

Animals↗

PubMedDate not supplied

Release of 5-fluorouracil from intramuscular w/o/w multiple emulsions.

Comparative in vivo studies of aqueous solution, multiple w/o/w, and w/o emulsions showed that formulating 5-fluorouracil in emulsion systems significantly sustained the release of the drug from intramuscular injection sites in the rat. Intramuscular injection of the drug in both w/o and w/o/w emulsion systems produced sustained blood concentrations with a later blood level peak than observed following intramuscular injection of aqueous solutions of the drug. The multiple w/o/w emulsion exhibited a more rapid release of drug from the injection site than the w/o emulsion because of partitioning of the drug to the external aqueous phase during secondary emulsification. The fate of the oil phase following intramuscular injection of a water/hexadecane/water multiple emulsion spiked with 1-14C-hexadecane has been studied in rats as a function of stabilizer concentrations. Increasing the lipophilic surfactant (Span 80) concentration facilitated the clearance of the oily vehicle from the injection site, by mechanisms which remain to be elucidated.

Animals↗

PubMedDate not supplied

In vitro release of adriamycin from drug-loaded albumin and haemoglobin microspheres.

Release of adriamycin from albumin and haemoglobin microspheres has been determined in vitro using a flow through system. Release from cross-linked albumin microspheres is controlled by the percentage of glutaraldehyde used but release profiles of spheres of 23, 41 and 60 microns diameter were virtually superimposable. Not all of the adriamycin is released from the microspheres over 20 h; as biodegradation occurs in vivo after 24 h the amount of drug remaining in the system at 20 h is likely to be principally released by degradation of the protein matrix in vivo. Estimates of the retained adriamycin vary from 16-26 per cent for albumin (n = 3) and 30 per cent for haemoglobin (n = 1).

Albumins↗

PubMedDate not supplied

The effect of niosomes and polysorbate 80 on the metabolism and excretion of methotrexate in the mouse.

The effect of non-ionic surfactant vesicle (niosome) encapsulation on the metabolism and urinary and faecal excretion of methotrexate (MTX) in mice has been studied following oral and intravenous administration, and compared with the effects of co-administration of free drug and polysorbate 80, which does not form vesicles. Niosome entrapment reduces the excretion of MTX into urine and bile whereas polysorbate 80 increases its excretion. Monitoring of the levels of MTX and its 7-hydroxy metabolite indicates that entrapped MTX is protected from rapid metabolism in vivo, particularly in niosomes but to a small degree in the micellar systems formed by polysorbate.

Administration, Oral↗

PubMedDate not supplied

Adriamycin-loaded niosomes: drug entrapment, stability and release.

The effect of encapsulation of adriamycin into niosomes, and its resultant chemical purity, was studied by means of HPLC and high-speed scanning spectrophotometry (the simultaneous use of which allowed investigation of potential non-fluorescent drug degradation products), and the process shown not to adversely affect the drug. Efficiency of entrapment of aqueous solutions of the drug was apparently dependent on neither vesicle composition nor method of production, and evidence of a degree of surfactant-adriamycin association was provided by the high entrapment values. Light-induced drug degradation was reduced by niosome encapsulation, and efflux of entrapped adriamycin was decreased by inclusion of cholesterol into the vesicles, in a manner similar to that reported for liposome preparations. Thus only chemically pure adriamycin was entrapped in, and released from, niosomes.

Doxorubicin↗

PubMedDate not supplied

Methotrexate transport from the internal phase of multiple w/o/w emulsions.

Release rates of Methotrexate (MTX) encapsulated in the internal phase of w/o/w emulsions stabilized by the interfacial interaction between albumin and sorbitan mono-oleate(Tween 80) were measured as functions of two formulation variables--the oil phase and the secondary emulsifier composition. The release rate was significantly affected by the nature of the oil phase and decreased in the order isopropyl myristate greater than octadecane greater than hexadecane greater than dodecane greater than octane, which was a reflection of the increasing internal droplet size of the emulsions. The release rate data conform with first order kinetics. Comparison of the effective permeability coefficients calculated from the experimental apparent first-order rate constants, with the effective permeability coefficient of water in planar oil layers, containing non-ionic surfactants, determined by a microgravimetric method supported the hypothesis of diffusion of MTX in water loaded inverse micelles. Surfactants with high HLB values, used as the secondary hydrophilic emulsifier increased the release rates, primarily by increasing the rate of diffusion of MTX through the non-aqueous liquid membrane.

Diffusion↗