The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.

Environmental monitoring programme in the cell therapy facility of a research centre: preliminary investigation.

INTRODUCTION: Recent discoveries in cell therapy research present new opportunities for cellular products to be used to treat severe, and as yet incurable, diseases. It is therefore essential to implement a quality control programme in order to ensure that safe cells and tissues are provided. METHODS: In a preliminary phase of the setting up of a the cellfactory, monitoring was carried out monthly over a 6-month period in one out of three cell therapy laboratories and filter rooms in order to evaluate the microbial contamination of air and surfaces and the presence of airborne particulates. RESULTS: The mean total bacterial and fungal loads measured in the air in the centre of the filter room were 20.7 +/1 28.9 colony-forming units (cfu)/m3 and 9.2 +/- 15.4 cfu/m3, respectively, and 5.2 +/- 4.1 cfu/m3 and 6.8 +/- 13.4 cfu/m3, respectively, in the laboratory. The mean fungal load values recorded on the surfaces sampled in the laboratory were in 6 out of 18 cases higher than the reference values (5 cfu/plate). As to the results of particulate monitoring, with regard to the 0.5 microm particles, about 83% of the samples revealed values below the limit of 350.000 particles per cubic metre. CONCLUSIONS: In this set-up phase, monitoring was able to pick out structural and organisational flaws acceptable in a laboratory compliant with Good Manufacturing Practices class C (Annex 1), but not in a class B facility. Thanks to this preliminary monitoring phase, and by correcting these flaws, the clean room facility could achieve compliance to class B.

Poloxamer 407 as a solubilising agent for tolfenamic acid and as a base for a gel formulation.

A solubility phase study was carried out to investigate the ability of Poloxamer 407 (P407) to solubilise tolfenamic acid. P407 considerably enhanced the solubility of this anti-inflammatory agent, by increasing its concentration in aqueous solution at least 2000-fold (up to C=4mM), when present at 12% (w/w) at 25 degrees C. The solubilisation process was spontaneous and exothermic, as indicated by thermodynamic parameters. A mixture experimental design was used to investigate the physical and release properties of P407-based gel formulations. The experimental design allowed verifying that drug release, occurring through a Fickian diffusion mechanism, was independent of the bulk viscosity of the system. The sustained release of tolfenamic acid towards the receptor phase constituted by isopropyl myristate was accompanied, in its early stage, by the concomitant release of ethanol and tetrahydrofurfuryl alcohol (THFA) used as cosolvents to obtain a drug loading of 0.6% (w/w). The poloxamer micellar phase was directly involved in the late stage of drug release, thus indicating that a strong interaction occurred in the gel between the poloxamer and tolfenamic acid. Results point out the possibility of both the systemic and topical administration of tolfenamic acid by means of aqueous solutions or gels containing P407 at an adequate concentration.

Chitosan-clodronate nanoparticles loaded in poloxamer gel for intra-articular administration.

This work was based on the study of an intra-articular delivery system constituted by a poloxamer gel vehiculating clodronate in chitosan nanoparticles. This system has been conceived to obtain a specific and controlled release of clodronate in the joints to reduce the arthritis rheumatoid degenerative effect. Clodronate (CLO) is a first-generation bisphosphonate with anti-inflammatory properties, inhibiting the cytokine and NO secretion from macrophages, therefore causing apoptosis in these cells. This is related to its ability to be metabolized by cells and converted into a cytotoxic intermediate as a non-hydrolysable analogue of ATP. Chitosan (CHI) was used to develop nanosystems, by ionotropic gelation induced by clodronate itself. A fractional factorial experimental design allowed us to obtain nanoparticles, the diameter of which ranged from 200 to 300nm. Glutaraldehyde was used to increase nanoparticle stability and modify the drug release profile. The zeta potential value of crosslinked nanopaparticles was 21.0mV±1.3, while drug loading was 31.0%±5.4 w/w; nanoparticle yield was 18.2%±1.8 w/w, the encapsulation efficiency was 48.8%±9.9 w/w. Nanoparticles were homogenously loaded in a poloxamer sol, and the drug delivery system is produced in-situ after local administration, when sol become gel at physiological temperature. The properties of poloxamer gels containing CHI-CLO nanoparticles, such as viscosity, gelation temperature and drug release properties, were evaluated. In vitro studies were conducted to evaluate the effects of these nanoparticles on a human monocytic cell line (THP1). The results showed that this drug delivery system is more efficient, with respect to the free drug, to counteract the inflammatory process characteristic of several degenerative diseases.

Preparation and evaluation of a chitosan salt-poloxamer 407 based matrix for buccal drug delivery.

The aim of this work was to prepare and evaluate a matrix for buccal drug delivery composed of a chitosan salt and poloxamer 407. Different chitosan salts were formed by reacting chitosan with acetic, citric, and lactic acid. Various proportions of poloxamer 407 were added to the aqueous solution of chitosan salt, and the residue obtained by lyophilisation was compressed into discs, using a 30 kN compression force. An experimental design (3(2)) was used to study the influence of the type of chitosan salt and of the relative amount of poloxamer on drug release capacity, swelling, erosion, and mucoadhesiveness of matrices. The results showed that matrix properties depended significantly on both relative amount of poloxamer and chitosan salt type. The rank orders of chitosan salts for the four processes evaluated were as follows: drug release: chitosan acetate>chitosan citrate>chitosan lactate; swelling: chitosan lactate>chitosan acetate=chitosan citrate; erosion: chitosan citrate>chitosan lactate>chitosan acetate; mucoadhesion: chitosan lactate>chitosan acetate=chitosan citrate. Mucoadhesion was particularly favoured when poloxamer 407 was present at about 30% (w/w). The matrix composed of chitosan lactate and poloxamer 407 showed the best characteristics for buccal administration.

Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in vivo studies.

The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

Species identification and confirmation of human and animal cell lines: a PCR-based method.

Misidentification and cross-contamination of cell lines are major problems of cell cultures that can make scientific results and their reproducibility unreliable. This paper describes a PCR-based method for easily identifying or confirming the species of origin of cell lines by using a panel of oligonucleotides specific for the nine animal species most common in cell culture laboratories. A panel of 35 human and animal cell lines, whose species of origin were previously confirmed by isoenzyme assay, was studied with nine species-specific primer pairs that specifically anneal to DNA sequences codifying for human, cat, dog, mouse, rat, horse, rabbit, African Green monkey cytochrome c oxidase subunit I (cox I), and one primer pair specific for the cytochrome b gene of Chinese hamster. The amplified fragments were analyzed by electrophoresis in ethidium bromide-stained 2% agarose gels. The method is simple, rapid, highly sensitive, and useful for routinely monitoring the species identity of cell cultures.

Polymorphism of the HLA-DP beta region detected by Southern blot hybridization.

A panel of homozygous cell lines, previously typed by primed lymphocyte test for their DPw specificity, have been studied by restriction fragment length polymorphism analysis, using a DP beta-specific probe. Highly stringent hybridization and washing conditions were used to prevent cross-hybridization with DR- and DQ-specific fragments. Three out of six enzymes employed allowed us to distinguish clustered or single DPw specificities, and by MspI digestion it was possible to detect different patterns within a single specificity such as DPw4. Some of the cell lines have been further studied with synthetic oligonucleotides derived from the polymorphic regions of the second exon of DP beta 1 gene, and, in general, a correlation with the primed lymphocyte test--defined specificities and restriction fragment length polymorphism was found. These data suggest a more extended complexity of the DP region, in addition to that defined as the DPw1-DPw6 segregant series.

Analysis and comparison of information and data recorded in carcinogenicity and genotoxicity databases.

The Interlab Project is a university-industry joint project recently funded by the Italian government as part of the improvement of the Italian research infrastructure; among its short-term goals are the implementation of data banks of biomedical interest and the spread of informatic tools for biomedical research. Results of both long-term assays of carcinogenicity in rodents and short-term in vitro and in vivo tests of genotoxicity are relevant for a wide body of users, ranging from carcinogenesis research laboratories to industries and governmental agencies. To evaluate the most appropriate ways of spreading information on these experiments, a detailed analysis on information recorded in available databases has been carried out. Furthermore, the contents of the most known databases have been compared, with respect to a specific compound, to evaluate both the overall reliability of these systems, compared to longer and more complex assessments carried out manually starting from bibliographic searches, and the level of concordance among them.

Cytotoxicity and cellular accumulation of a new cis-diammineplatinum (II) complex containing procaine in murine L1210 cells sensitive and resistant to cis-diamminedichloroplatinum (II).

The emergence of drug resistance during tumor chemotherapy is one of the main problems associated with cancer treatment, particularly with cisplatin (cis-DDP). In the hope of overcoming this problem, various cis-DDP-derived compounds have been synthesized, and their pharmacological activity was compared with that of cis-DDP. In this paper we report on studies on the cytotoxic activity induced by cis-diamminechloro-[2-(diethylamino)ethyl-4-aminobenzoate, N4]- chlorideplatinum(II) monohydrochloride monohydrate (DPR), a new complex of platinum containing procaine. All experiments were carried out on murine leukemic cells, which were either sensitive (L1210) or resistant (L1210/DDP) to cis-DDP. A tetrazolium dye (MTT) assay conducted 5 days after a 2-h exposure of cells to both drugs was utilized to determine the resistance factor (RF) of L1210/DDP cells as compared with the sensitive wild-type cells. Drug accumulation and efflux, together with the amount of platinum bound to DNA, were also investigated. The activity of DPR on sensitive cells was not significantly different from that of cis-DDP. Conversely, DPR was 4.3 times more effective than cis-DDP on resistant cells. A decreased drug accumulation is one of the mechanisms of resistance to cis-DDP of L1210/DDP cells. However, DPR accumulation was not significantly different in sensitive and resistant L1210 cells. Under culture conditions that yielded similar intracellular platinum concentrations, treatment with DPR produced significantly greater DNA platination than did treatment with cis-DDP in both cell lines. No difference in efflux was observed between L1210 and L1210/DDP cells exposed to either cis-DDP or DPR. Our results show that in parental cells, DPR is as potent as cis-DDP on a molar basis, and it is also minimally cross-resistant with cis-DDP in L1210/DDP cells. A direct implication of our results is that DPR could be useful in those human tumors showing a mechanism of resistance similar to that of L1210/DDP cells.

Chemical and biological properties of a new cis-diammineplatinum (II) complex containing para-aminobenzoic acid as amino ligand.

In this paper we report on the synthesis, characterization and preliminary pharmacological evaluation of a new platinum (II) complex obtained by reaction of cis-diamminedichloroplatinum(II) (DDP) with para-aminobenzoic acid (PABA). The structure of this platinum compound was defined by UV, IR, 1H-NMR and elemental analysis. DPAB tested in vitro and in vivo against P388 leukemic cells displayed good antiproliferative (IC50 values after 48 h exposure of cells = 3 micrograms/ml) and antitumor activity (T/C% = 150). This compound also possesses desirable physical properties, such as a good solubility and stability in aqueous media, and a low toxicity (LD50 > 1200 mg/kg body weight) combined with a moderate nephrotoxic activity [plasma urea nitrogen (PUN) level: 36 +/- 8(SD) mg/100 ml]. DPAB was cleared from plasma ultrafiltrate (UF-plasma) very rapidly [clearance (CL), 55.3 ml x min-1 x kg-1], showing a half-life of 13.6 min. Platinum exposure (AUC) in the kidney was 2.6 times greater than that found in UF-plasma. AUCS for liver, stomach and UF-plasma were similar, while the AUC value for the spleen was 1.7 times lower than that of UF-plasma. These preliminary results seem to hold interest for further preclinical evaluation of the biological activity of this new platinum compound.

Effect of normal saline on cisplatin pharmacokinetics and antitumor activity in mice bearing P388 leukemia.

The effect of normal saline (NS) on the antitumor activity, toxicity and pharmacokinetic of cisplatin (DDP) was investigated in BDF1 mice bearing P388 leukemia. Tumor-bearing mice received 8 or 16 mg/Kg of DDP dissolved in NS or distilled water (DW) intraperitoneally. Control animals were treated with DW or NS alone. The administration of 8 mg/Kg of DDP+NS produced a significantly better survival (P less than 0.05) compared to that observed in mice receiving DDP+DW. The proportion of long-term survivors was 3.5 times higher in the DDP+NS group (39%) compared to the DDP+DW group (11%). The administration of 16 mg/kg DDP+DW was highly toxic, resulting in early deaths (MST = 5 days) and no long-term survivors. NS protected from DDP toxicity without further improving the survival achieved following the injection of 8 mg/kg DDP+NS. Investigation of platinum pharmacokinetics showed that NS significantly decreases both plasma and tissue concentrations of total platinum, mainly through a decrease in the amount of platinum bound to high molecular weight plasma proteins. HPLC studies indicated that mice receiving 8 mg/kg DDP+NS or DDP+DW fail to show clear differences both in the total ultrafilterable platinum and unchanged DDP in plasma ultrafiltrate. Conversely, mice treated with DDP+NS had higher concentrations of platinum-species in plasma ultrafiltrate than mice receiving DDP+DW. These latter results, together with the observation that NS decreases the amount of platinum bound to plasma proteins, suggest that the effect of NS does not solely depend in vivo on the ability of the chloride ion concentration to stabilize the DDP molecule and suppress the formation of DDP metabolites, but also on its ability to prevent DDP toxicity by reducing the protein binding of DDP aquated products.

Synthesis and antitumor activity of a new cis-diammineplatinum (II) complex containing procaine hydrochloride.

This paper refers to some of the chemical and biological properties of a new platinum (II) complex where the aromatic amino group of procaine is involved in the coordination with platinum and whose structure was defined by UV, IR, 1H-NMR, and elemental analysis. This new cationic platinum-triamine complex (DPR) displays excellent solubility (> 50 mg/ml) and stability in water. DPR has significant in vitro cytotoxicity against murine P388 leukemic cell line, human K562 erythroleukemic cell line and human Jurkat T cell line. The in vitro cytotoxic effects of DPR on P388 and Jurkat leukemic cells were comparable to those of cis-diamminedichloroplatinum (II) (DDP), while its activity on K562 cells was significantly better than that of DDP [IC50 = 1.07 +/- 0.36 (SD) microM vs 2.62 +/- 0.23 (SD) microM, P < 0.01]. The in vitro Pt accumulation rate for P388 cells was twice as rapid after DPR than after DDP exposure, while no difference in cellular platinum efflux was observed. The antitumor activity of DPR was tested in vivo against P388 leukemic cells in BDF1 mice and gave a % ILS value (75%) similar to that of the maximum tolerated dose (MTD) of DDP (8 mg/Kg). A comparative study of plasma urea nitrogen (PUN) levels and kidney morphological analysis in tumor-bearing mice receiving the LD50 dose of both drugs (39.3 mg/Kg and 16.5 mg/Kg for DPR and DDP, respectively), showed DPR to be less nephrotoxic than DDP. These results indicate that this new cationic platinum-triamine complex containing primary amine ligand is surprisingly active both in vitro and in vivo. In summary, the good characteristics of DPR in terms of high solubility, encouraging anticancer activity and absence of nephrotoxic effects make DPR a promising new platinum anticancer agent for preclinical development.

Serum, urine and peritoneal fluid levels of 5-FU following intraperitoneal administration.

Seven patients with advanced colon cancer, refractory to conventional chemotherapy, and malignant disease confined to the intra-abdominal space received a total of 24 consecutive courses of ip 5-Fluorouracil (5-FU). 5-FU 1000 mg was administered in 2 L of warm (37 degrees C) dialysate daily for five consecutive days every 28 days. 5-FU concentrations in serum, peritoneal fluid and urine were measured by high pressure liquid chromatography (HPLC). The mean disappearance half-life of 5-FU from the peritoneal fluid was 1.6 hours with a mean permeability area product (PA) of 22.4 ml/min. The mean peritoneal AUC was 450 +/- 165 times greater than the mean serum AUC. Ip 5-FU treatment is well tolerated, can be safely administered on an outpatient basis and produces a significant pharmacological advantage over conventional routes of administration.

Cis-diamminedichloroplatinum (II)-procaine pharmacokinetic interaction in mice bearing P388 leukemia.

The distribution and elimination kinetics of cis-diamminedichloroplatinum (II) (DDP) in female BDF1 mice bearing 6-day P388 leukemia were investigated in the presence and absence of procaine hydrochloride (P.HCl) exposure. DDP was administered as a single i.p. dose of 8 mg/kg in a 0.9% NaCl solution 6 days after tumor inoculum. P.HCl was administered as a single i.v. dose of 40 mg/kg immediately after DDP. The combined treatment with P.HCl produced marked changes in the plasma concentration-time profile of Pt. The unbound fraction of Pt was significantly increased both in the ascites fluid and plasma following DDP + P.HCl administration. P.HCl treatment induced a significant reduction (P < 0.01) in the rate constant of the protein-bound of Pt in plasma of tumored mice. Urinary excretion of Pt was unaffected by P.HCl, and there was no significant P.HCl-induced modification in the concentrations of Pt in the P388 leukemic cells. A statistically significant reduction of kidney and spleen Pt content was observed in female mice exposed to a dose of 8 mg/kg DDP + P.HCl. A similar reduction was observed in kidneys and testes of tumored mice receiving 16 mg/kg DDP along with 40 mg/kg P.HCl, which also showed lower renal and testicular cisplatin-DNA adducts after DDP + P.HCl than after DDP treatment. Potential explanations for the ability of P.HCl to interfere with the pharmacokinetics and biodistribution of DDP are discussed.

Median-based robust regression methods in prediction of drug stability.

The classical isothermal approach for the prediction of drug stability exploits least squares regression. In this paper the use of some robust regression techniques to estimate the rate constants at different temperatures has been evaluated. These techniques are able to give accurate estimates when data are contaminated by the presence of outliers. The successful application of two robust methods, single median and repeated median, to real stability data from the literature is shown. Moreover, the authors have modified the original methods in order to apply them to data sets with replicates, typical of stability studies. The performances of the modified techniques have been investigated with simulated data sets containing outliers and with real data. They appear suitable for preliminary stability studies, especially on solid dosage forms. For a quick implementation of these methods, macroprograms written for a widely used spreadsheet are reported.

Study of the interaction of dithranol with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin in solution and in the solid state.

The interaction between dithranol and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMBCyD) has been investigated in aqueous solution containing isoascorbic acid (0.2% w/v) as antioxidant and in the solid state. The interaction in the solid state was studied by differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XPD) and a dissolution-rate method. The extent of complexation between the two substances was poor, as indicated by the low value of the slope of the linear part of the solubility curve. A phase diagram was constructed by measuring the thermal behaviour of various re-solidified physical mixtures of dithranol and of TMBCyD previously subjected to heating until melting of the TMBCyD. The loss of dithranol, owing to sublimation and degradation caused by the thermal treatment used, was less than 10%. In keeping with XPD and IR data, the phase diagram indicated that a complex was formed containing 13.7% dithranol (molar ratio 1:1) which had a congruent melting point at 164 degrees C. The drug dissolution rate from the 1:1 complex was measurable, unlike that of the corresponding physical mixture, and was significantly increased when the complex was dispersed in the glassy matrix of TMBCyD, as it was in re-solidified mixtures containing 2-7% dithranol. The results show that the solubility of dithranol is increased significantly as a consequence of its interaction with TMBCyD, despite the low extent of complexation between the two substances.

Herbal mixtures with claimed slimming activity: determination by TLC and HPLC of illegally added drugs.

A method for the detection and quantitation of several undeclared drugs in herbal preparations with slimming activity is proposed. Samples containing various anorexics, hypoglycemics and antidepressants were prepared by addition of the drugs to a synthetic mixture containing the most commonly used plant powders for those preparations. Each sample was subjected to a treatment that permitted, after a simple ethanolic extraction, the identification of the drugs by TLC using three different solvent systems. A further purification of the ethanolic solution through a polyamide column allowed for quantitative analysis of the drugs by a RP-HPLC method. The analytical recovery was good (88-97%); the calibration curves were linear over a wide range of drug concentrations (30-500 micrograms/ml) (r > 0.9995); the precision was high (CV% = 0.4-2.8) as well as the accuracy (96-102%).

[Surgical implications of familial polyposis coli]. / Implicazioni chirurgiche della poliposi familiare del colon (PFC).

Surgical treatment of familial congenital polyposis (FCP) is deemed necessary as soon as diagnosis is obtained. The goals of any surgical procedure must be: removal of all adenomatous tissue, reliable prophylaxis of cancer, good quality of life. Among the different procedures (proctocolectomy with ileostomy, total colectomy with ileo-rectal anastomosis and postoperative endoscopic surveillance, ileo-rectal pull-through) we consider Soave ileo-endorectal pull-through as the treatment of choice. Between 1974 and 1993, 14 patients, 12 to 40 years old, underwent an ileo-endorectal pull-through (in 4 cases as secondary procedure after ileo-rectal anastomosis performed elsewhere). We had only two major complications, ileal perforation in one case and breakdown of ileo-rectal anastomosis in another case that needed permanent ileostomy. Continence is good in all patients (safe for the one with ileostomy) with an average of three bowel movements per day. Prophylaxis of cancer must be considered complete and permanent without need of surveillance.

Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles.

A new nanoparticulate system for foscarnet delivery was prepared and evaluated. Nanoparticles were obtained by ionotropic gelation of chitosan induced by foscarnet itself, acting as an ionotropic agent in a manner similar to tripolyphosphate anion. A Doehlert design allowed finding the suitable experimental conditions. Nanoparticles were between 200 and 300nm in diameter (around 450nm after redispersion). Nanoparticle size increased after 5h, but no size increase was observed after 48h when nanoparticles were crosslinked with glutaraldehyde. Zeta potential values of noncrosslinked and crosslinked nanoparticles were between 20 and 25mV, while drug loading of noncrosslinked nanoparticles was about 40% w/w (55% w/w for crosslinked nanoparticles). Nanoparticle yield was around 25% w/w. Crosslinked nanoparticles showed a controlled drug release. Foscarnet released from nanoparticles maintained the antiviral activity of the free drug when tested in vitro against lung fibroblasts (HELF) cells infected with HCMV strain AD-169. Moreover, nanoparticles showed no toxicity on non-infected HELF cells. These nanoparticles may represent a delivery system that could improve the therapeutic effect of foscarnet.