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P P Deluca

Publications and source records attributed to P P Deluca.

11 recordsLinked to original sources
PubMed2004

In vitro cytotoxicity of mitoxantrone-incorporated albumin microspheres on acute promyelocytic leukaemia cells.

In the present study, the preparation and characterization of bovine serum albumin (BSA) microspheres and the evaluation of the in vitro cytotoxicity of these microspheres on acute promyelocytic leukaemia (HL-60) cells were described. Mitoxantrone (MTZ)-incorporated microspheres were evaluated for particle size, drug loading, release characteristics and surface morphology. The biological effect of MTZ released from BSA microspheres was determined on an in vitro cultured HL-60 cell line, showing that, after encapsulation, MTZ still retains cytotoxic activity. For this purpose, methyl-thiazol-tetrazolium (MTT) assay was used to evaluate the in vitro cytotoxicity of MTZ-loaded microspheres. Particle size of BSA microspheres was determined between 17.61-20.38 microm and they were smooth and spherical in shape. Encapsulation efficiency of the drug-loaded microspheres was between 22.26-60.50%. For MTZ-containing microspheres, the cell death ratios were greater than 80% for all formulations. This study demonstrate that BSA microspheres were well suited for the controlled release of MTZ and were promising for anti-cancer chemotherapy.

Animals↗
PubMed2000

Pharmacokinetic disposition of polyethylene glycol-modified salmon calcitonins in rats.

This study first reports the pharmacokinetic disposition of polyethylene glycol (PEG)-modified salmon calcitonin (sCT) based on the number of attached PEG molecules. PEG-modified sCT was prepared by covalent linkage with succinimidyl carbonate monomethoxy polyethylene glycol. Mono- and di-PEG-sCTs were separated by size exclusion and reverse phase HPLC, and radioiodinated by the chloramine-T method with Na125I. 125I-mono-PEG sCT, 125I-di-PEG-sCT and unmodified 125I-sCT were administered to rats by i.v. injection. Serial blood samples, urine and various tissue samples were taken for the determination of radioactivity. Di-PEG-sCT exhibited significantly reduced systemic clearance (2.3 vs. 11.1 ml/min/kg) and steady-state volume of distribution (229.9 vs. 603.1 ml/kg), while mono-PEG-sCT showed a prolonged elimination half-life (189.1 min vs. 59.8 min) compared with unmodified sCT. The extent of urinary excretion of the PEG-modified sCTs was higher than for the unmodified sCT, but all these chemicals were excreted in urine in small quantities (< or = 0.6%). There was a tendency toward reduced accumulation of PEGylated sCTs in tissues, with its reduction being inversely proportional to the molecular size. Accumulation of the total radioactivity of the unmodified and PEG-modified sCTs was highest in the liver, followed by kidneys, lungs, spleen, heart and thyroid. When expressed per tissue gram weight, however, the highest radioactivity was found in the kidneys. PEGylated sCTs may have greater therapeutic potential via reduced systemic clearance and prolonged elimination half-life over unmodified sCT.

Animals↗
PubMed1981

Co-mutagenic effects of 2-aminoanthracene and cigarette smoke condensate on smoker's urine in the Ames Salmonella assay system.

Cigarette smoke condensate (CSC) and cigarette smoker's urine (concentrated) (UC) were tested alone and in combination with direct and indirect mutagens for histidine reversion in the Ames Salmonella assay system. While both CSC and smoker's urine showed some mutagenic activity upon metabolic activation with S9-mix, each of them in combination with the aromatic amine 2-aminoanthracene (2AA) exhibited a synergistic effect on mutagenicity. Such a synergistic effect was not found when these agents were combined with the direct mutagens, ethylmethane sulfonate (EMS) and methylmethane sulfonate (MMS), or the indirect mutagens, benzo[a]pyrene (BP) and 9,10-dimethyl-1,2-benzanthracene (DMBA), tested in this study, nor was the synergistic effect observed when 2AA was tested with urine from a non-smoker. The results, thus, reflected a specificity of the co-mutagenic action of factor(s) in cigarette smoke or smoker's urine and 2AA. The significance of co-mutagens in carcinogenesis has been discussed and the importance of investigating co-mutagenesis particularly in the case of suspected human exposure to multiple environmental agents has been emphasized.

Anthracenes↗
PubMedDate not supplied

Effect of gamma-irradiation on peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) microspheres.

The effect of gamma-irradiation on the physicochemical properties of peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) (PLGA) microspheres was evaluated. PLGA (50/50, Mw: 8,600) with free carboxylic end groups was used to make drug-loaded and placebo microspheres by a solvent extraction evaporation method. Both formulated and non-formulated microspheres were gamma-irradiated at 0, 1, 1.5, and 2.5 Mrad doses. HPLC analysis based on extraction of peptide from the microspheres showed that peptide content of the microspheres was lowered upon irradiation and the reduction was more pronounced in formulated microspheres. The in-vitro release in 0.033M phosphate buffer, pH 7.0 at 37 degrees C (based on extraction of residual peptide) showed that the initial and subsequent release of peptide was higher in gamma-irradiated microspheres during the first 20 days. The difference became insignificant during the erosional controlled release of the peptide. There was no difference in release between the formulated and non-formulated microspheres of the nonirradiated or irradiated forms. Molecular weights (Mw and Mn), determined by size exclusion chromatography, were reduced by gamma-irradiation for both formulated and non-formulated placebo microspheres. Differential scanning calorimetry showed a gradual reduction in Tg of placebo microspheres but no reduction in peptide-loaded microspheres. In-vivo evaluation of the nonirradiated and the 1.5 Mrad irradiated microspheres showed no marked differences through 28 days. Since irradiation caused a lowering of Mw and Mn with the appearance of a low amount of unidentified substances, seemingly catalyzed by the polymer and the formulation excipients, gamma-irradiation sterilization of these parenteral delivery systems requires careful investigation on an individual product basis.

Gamma Rays↗
PubMedDate not supplied

Rheological characterization of cellulosic and alginate polymers.

The purpose of this study was to assess the properties of aqueous solutions of various polymeric materials intended for use as components of a sustained release device for various proteins. Polymers that were studied included Sodium Carboxymethylcellulose (CMC), Methylcellulose (MC), Hydroxypropylmethylcellulose (HPMC) and Sodium Alginate (ALG). The effects of polymer concentration, temperature and autoclaving on solution viscosity were determined. With all the polymers, viscosity/ concentration relationships were linearized by using an equation of the type mu = (Ca + beta)gamma, where mu and C referred to solution viscosity and concentration, respectively. alpha and gamma were constants related to polymer type and molecular weight, whereas beta reflected viscosity of water at the temperature of measurement. gamma, which reflects the sensitivity of the viscosity/concentration relationship, was determined to be 4 for both low and high molecular weight CMC and ALG, and 8 for MC and HPMC. alpha, on the other hand, was directly proportional to polymer molecular weight. The same equation could also adequately describe viscosity/temperature relationships for each polymer. For both CMC and ALG, increasing solution concentration had a greater effect on the reduction of viscosity upon increasing temperature. A concentration dependent thermal "gelation" phenomena was observed with MC solutions. Autoclaving effects were more pronounced in ALG solutions as compared to CMC samples in the 0.5 to 3.0% w/v concentration range. No significant long term effects on solution viscosity were observed with MC and HPMC, however.

Alginates↗
PubMedDate not supplied

Buffer uptake and mass loss characteristics of freeze-dried cellulosic and alginate devices.

The buffer uptake and mass loss characteristics of freeze dried unitary devices prepared from aqueous solutions of Sodium Carboxymethylcellulose (CMC), cross-linked Sodium Alginate (ALG) and Methylcellulose (MC) were evaluated. Some of the devices also contained 50% (by weight) Poly (d,l Lactide-co-Glycolide) (PLGA) microspheres. Devices prepared from cross-linked ALG solutions imbibed the highest amounts of isotonic Phosphate Buffered Saline, followed by those from prepared from CMC solutions, and lastly, MC. In all cases, the presence of microspheres within the devices significantly decreased buffer uptake. Uptake was determined to be approximately proportional to the weight percent of the hydrophilic matrix polymer. Highest levels of overall mass loss were observed with devices prepared from cross-linked ALG solutions (approximately 80% in 60 days), followed by those prepared from CMC solutions (approximately 45 to 65%) and MC (approximately 35 to 60%). A majority of the unitary devices retained their shape and integrity, however, over the two month test period, indicating possible use as long term delivery systems for incorporated bone growth factors.

Alginates↗