Properties Of Drug Carriers Research Articles

Poly(ethylene carbonate)s, part II : degradation mechanisms and parenteral delivery of bioactive agents

The degradation and drug carrier properties of poly(ethylene carbonate) (PEC) were investigated in vitro and in rats and rabbits. PEC was found to be specifically degraded in vivo and in vitro by superoxide radical anions O 2 −·, which are, in vivo, mostly produced by inflammatory cells. No degradation of PEC was observed in the presence of hydrolases, serum or blood. PEC is biodegraded by surface erosion without significant change in the molecular weight of the residual polymer mass. The non-hydrolytic biodegradation by cells producing O 2 −· is unique among the polymers used as biodegradable drug carriers. The main degradation product of PEC in aqueous systems is ethylene glycol, formed presumably by hydrolysis of ethylene carbonate. The splitting off of a five-membered ring structure from the polymer chain indicates a chain reaction mechanism for the biodegradation. PEC is a suitable drug carrier, particularly for labile drugs. Using human interleukin-3 and octreotide as model drugs, surface erosion of the PEC formulations was indicated by a 1:1 correlation between drug release and polymer mass loss.

Extravasation of poly(amidoamine) (PAMAM) dendrimers across microvascular network endothelium.

To study the influence of a controlled incremental increase in size and molecular weight of a series of poly(amidoamine) (PAMAM) dendrimers on their extravasation across the microvascular network endothelium. A series of PAMAM dendrimers (generations 0-4) were fluorescently labeled using fluorescein isothiocyanate (FITC). Purification and fractionation of the fluorescently labeled polymers were done using size exclusion chromatography. The hamster cremaster muscle preparation was used as an in vivo model to study the extravasation process of the fluorescently labeled polymers. The extravasation process was visualized and recorded using intravital microscopy techniques. Analysis of the recorded experiments was done using Metamorph Imaging System. Extravasation of the fluorescently labeled polymers is reported in terms of their extravasation time (tau), i.e., the time needed for the fluorescence intensity in the interstitial tissue to reach 90% of the fluorescence intensity in the neighboring microvessels. Extravasation time (tau) describes the rate of microvascular extravasation of polymeric drug carriers across the microvascular endothelium into the interstitial tissue. Extravasation time (tau) of the studied PAMAM dendrimers showed size and molecular weight dependence. An increase in size and/or molecular weight of PAMAM dendrimers resulted in a corresponding exponential increase in the extravasation time (tau). Extravasation of PAMAM dendrimers across the microvascular endothelium showed size and molecular weight dependence. Results suggest that in addition to size and molecular weight, other physicochemical properties of polymeric drug carriers such as molecular geometry and charge may influence their microvascular extravasation. Systematic studies of the influence of the physico-chemical properties of polymeric drug carriers on their microvascular extravasation will aid in the design of novel macromolecular drug carriers with controlled extravasation profiles.

The Physical Properties of Biogels and their Permeability for Macromolecular Drugs and Colloidal Drug Carriers

Macromolecular drugs, either free or complexed with colloidal drug carriers, have created a great deal of interest during the last decade. If one wants to administer these new therapeutics via the oral, nasal, and cervical routes or through the conductive airways, one of the first barriers to overcome is the mucus layer that adheres to the related epithelia. In this review, the physicochemical properties of biogels, macromolecular drugs, and colloidal drug carriers that play a major role in transport through biogels are reviewed. Also, methods of studying the mobility of macromolecular drugs and colloidal drug carriers in and through biogels are addressed. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89:835–849, 2000

Magnetic drug targeting. II. targeted drug transport by magnetic microp articles: factors influencing therapeutic effect

The kinetic aspects of magnetically targeted drug transport are considered. The influence of the magnetic drug carrier properties, the transported drug and the target parameters on the biological effect of the drug is discussed. The mathematical model reflecting the mass-transfer processes in a blood flow system is used for the estimation of the influence of these factors on the therapeutic effect of the drug delivered to the target. The character of the effect of drug release parameters, rate of drug released inactivation and the intensity of carrier capture in the liver is shown. Mathematical modelling of magnetically targeted drug kinetics allows possibilities for prognosis of drug effects.

Solution properties of drug carriers based on poly[N‐(2‐hydroxypropyl)methacrylamide] containing biodegradable bonds

AbstractThe solution properties of water‐soluble drug carriers based on copolymers of N‐(2‐hydroxypropyl)methacrylamide containing p‐nitroaniline (drug model) attached to the copolymer by enzymatically degradable oligopeptide chains, were studied using light scattering, GPC and sedimentation methods. It was found that these polymers associate in water forming micelles with p‐nitroaniline being inside and hydrophilic polymer chains outside. The association number and compactness of micelles both depend on the content of hydrophobic side chains, polymer concentration and temperature. Micellar shells hinder the penetration of enzymes into the micellar core, thus reducing the rate of enzyme‐catalyzed release of p‐nitroaniline.

Biomedical applications of magnetic fluids III. Antitumour effect of magnetic albumin microsphere-entrapped adriamycin on lung metastasis of AH 7974 in rats

Drug carrier properties of magnetic albumin microspheres containing adriamycin were determined. Magnetic microspheres exhibited sustained drug release and could be guided into a target site in vivo (lung) by magnetic means. Enhancement of antitumour effects of adriamycin on AH 7974 lung metastasis in rats was exhibited by administration of the magnetic microspheres and subsequent exposure of a magnetic field to the lungs. These results suggest that magnetic albumin microspheres may be applicable as a drug carrier with site specificity in cancer chemotherapy.

Poly(L-lysine) has different membrane transport and drug-carrier properties when complexed with heparin.

Methotrexate (MTX) conjugated to a Mr 3000 poly(L-Lys) markedly inhibits the growth of Pro-3 MtxRII5-3 Chinese hamster ovarian cells, a mutant line known to be drug resistant because of defective MTX transport. In these cells, membrane transport of [3H]MTX-poly(Lys) is sharply decreased by addition of 0.5- to 2.5-fold heparin but remains at 15-20% of control in 2.5- to 50-fold heparin excess. Heparin addition at first markedly inhibits but, at high concentration, restores the growth inhibitory effect of MTX-poly(Lys). In excess heparin, MTX-poly(Lys) is transported as a heparin complex. Because reduced transport (15-20%) is sufficient to cause a 90% inhibition of cell growth, MTX-poly(Lys) apparently gains pharmacologic potency when compared to heparin. This gain can be related to a greater inhibitory effect on dihydrofolate reductase and to a different mode of transport. The inhibitory effect of MTX-poly(Lys) on dihydrofolate reductase in vitro is increased nearly 100-fold in the presence of excess heparin but remains less than that of free MTX. Unlike that of MTX-poly(Lys), the transport of MTX-poly(Lys)-heparin has the characteristics and efficiency of a receptor-mediated process. It proceeds by endocytosis but is not, as in the case of uncomplexed conjugate, followed by the intracellular generation of pharmacologically active breakdown products that would account for cytotoxicity. These observations raise the possibility that at least part of the MTX-poly(Lys)-heparin reaches cellular dihydrofolate reductase in the form of macromolecular complexes that escape from entrapment in endocytotic structures. Our data illustrate a way to overcome drug resistance by taking advantage of the specific uptake of a macromolecular drug carrier. They offer a method of drug delivery in which heparin improves selectivity and decreases the unwanted toxicity inherent to polycationic carriers.

Drug-carrier property of albumin microspheres in chemotherapy. V. Antitumor effect of microsphere-entrapped adriamycin on liver metastasis of AH 7974 cells in rats.

Drug-carrier property of albumin microspheres in chemotherapy. V. Antitumor effect of microsphere-entrapped adriamycin on liver metastasis of AH 7974 cells in rats.

Drug-carrier property of albumin microspheres in chemotherapy. IV. Antitumor effect of single-shot or multiple-shot administration of microsphere-entrapped 5-fluorouracil on Ehrlich ascites or solid tumor in mice.

Drug-carrier property of albumin microspheres in chemotherapy. IV. Antitumor effect of single-shot or multiple-shot administration of microsphere-entrapped 5-fluorouracil on Ehrlich ascites or solid tumor in mice.

Drug-carrier property of albumin microspheres in chemotherapy. II. Preparation and tissue distribution in mice of microsphere-entrapped 5-fluorouracil.

Bovine serum albumin microspheres contatining 5-fluorouracil-6-3H were prepared by heating at 180° (or 150°, 100°) of 25% albumin solution in cottonseed oil emulsion. The shape of this microsphere was invariably spherical, and the average diameter was 0.66μ. After intravenous injection in mice, 5-fluorouracil-6-3H entrapped in albumin microspheres localized mainly in the liver, and the disappearance rate of radioactivity in microspheres from the tissue was very slow in comparison with that of free drugs. The microsphere might be delivered into reticuloendothelial system in the liver because ofits phagocytic activity, as well as the distribution following injection of albumin macroaggregates. Such preferential localization and sustained release of entrapped drugs suggested that albumin microspheres are useful as drug-carrier in chemotherapy.

Drug-carrier property of albumin microspheres in chemotherapy. III. Effect of microsphere-entrapped 5-fluorouracil on ehrlich ascites carcinoma in mice.

To examine the possibility of utilizing albumin microspheres as drug-carriers, an in vitro release of 5-fluorouracil (5-FU) from albumin microspheres was examined and the effect of intraperitoneally injected drug-carrying microspheres on Ehrlich ascites carcinoma in mice was studied. In vitro release characteristics determined by dialysis experiments showed that 5-FU release continued over one week. We also noted that drug release in the peritoneum of ascites-bearing mice continued over one week and that their life-span increased. Furthermore, the microspheres were phagocytized in vivo by the ascites cells. Our results suggest that albumin microspheres containing 5-FU may represent an effective system of drug delivery with prolonged action.

Drug-carrier property of albumin microspheres in chemotherapy. I. Tissue distribution of microsphere-entrapped 5-fluorouracil in mice.

Drug-carrier property of albumin microspheres in chemotherapy. I. Tissue distribution of microsphere-entrapped 5-fluorouracil in mice.