Use Of Oral Formulations Research Articles

Vesicular drug delivery systems for oral absorption enhancement

Oral administration is the most acceptable route of drug delivery at this stage due to its convenience, safety, and non-invasiveness. However, drugs given orally are exposed to a complex gastrointestinal environment, causing a tremendous challenge for their successful absorption into the circulation. Over the past decades, researchers have developed various novel pharmaceutical technologies to improve oral absorption, among which the vesicular drug delivery system (like liposomes, niosomes and transfersomes) has received extensive attention. Encouragingly, there have been several investigations confirming the improved effect of vesicular drug delivery systems on oral drug absorption. Nevertheless, the clinical translation of oral vesicular drug delivery systems has been less impressive than implied by the positive results, and few vesicular formulations for oral use have been marketed yet. Against this background, this article provides an overview of the current applications and challenges associated with the vesicular delivery systems available for oral drug delivery, specifically liposomes, niosomes, transfersomes, chitosomes and bilosomes. The composition, formation mechanism, drug delivery advantages and application cases of these carriers in oral drug delivery are summarized. The possible mechanisms by which vesicular carriers enhance oral drug absorption are analyzed in terms of the in vivo process of oral drugs. Further, the challenges that oral vesicular carriers now face, such as safety, undefined in vivo fate, and scale-up production, are summarized, while possible strategies to deal with them are indicated. By reviewing the aforementioned, it can facilitate a more comprehensive knowledge of vesicular systems that can be used for oral drug delivery, providing a theoretical basis and reference for the design of oral formulations.

Cinchonine, a Potential Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist, Lowers Blood Glucose and Ameliorates Non-Alcoholic Steatohepatitis.

The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). Research has focused on small-molecule GLP-1R agonists because of their ease of use in oral formulations and improved patient compliance. However, no small-molecule GLP-1R agonists are currently available in the market. We aimed to screen for a potential oral small-molecule GLP-1R agonist and evaluated its effect on blood glucose and NASH. The Connectivity map database was used to screen for candidate small-molecule compounds. Molecular docking was performed using SYBYL software. Rat pancreatic islets were incubated in different concentrations glucose solutions, with cinchonine or Exendin (9-39) added to determine insulin secretion levels. C57BL/6 mice, GLP-1R-/- mice and hGLP-1R mice were used to conduct oral glucose tolerance test. In addition, we fed ob/ob mice with the GAN diet to induce the NASH model. Cinchonine (50 mg/kg or 100 mg/kg) was administered orally twice daily to the mice. Serum liver enzymes were measured using biochemical analysis. Liver tissues were examined using Hematoxylin-eosin staining, Oil Red O staining and Sirius Red staining. Based on the small intestinal transcriptome of geniposide, a recognized small-molecule GLP-1R agonist, we identified that cinchonine exerted GLP-1R agonist-like effects. Cinchonine had a good binding affinity for GLP-1R. Cinchonine promoted glucose-dependent insulin secretion, which could be attenuated significantly by Exendin (9-39), a specific GLP-1R antagonist. Moreover, cinchonine could reduce blood glucose in C57BL/6 and hGLP-1R mice, an effect that could be inhibited with GLP-1R knockout. In addition, cinchonine reduced body weight gain and food intake in ob/ob-GAN NASH mice dose-dependently. 100 mg/kg cinchonine significantly improved liver function by reducing the ALT, ALP and LDH levels. Importantly, 100 mg/kg cinchonine ameliorated hepatic steatosis and fibrosis in NASH mice. Cinchonine, a potential oral small-molecule GLP-1R agonist, could reduce blood glucose and ameliorate NASH, providing a strategy for developing small-molecule GLP-1R agonists.

Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists.

IntroductionCancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer.MethodsAn anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents’ regions, case volumes, and practice type were explored.ResultsOf 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents’ region and case volume were noted.ConclusionMedical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40487-022-00191-7.

Arsenic trioxide inhibits anaplastic lymphoma kinase (ALK)‐positive diffuse large B‐cell lymphoma through targeting ALK‐fusion oncoprotein

Arsenic trioxide inhibits anaplastic lymphoma kinase (ALK)‐positive diffuse large B‐cell lymphoma through targeting ALK‐fusion oncoprotein

Retrospective survey of compounded medications for children in Japan

Compounding of medications, such as crushing tablets and dispersing the contents of capsules, is a common practice in pharmacies and hospitals worldwide and is often done to provide age-appropriate formulations for oral use in pediatric patients. In the present study, a retrospective, descriptive, questionnaire-based survey was conducted to clarify the current status of drug compounding for pediatric patients in Japan. An electronic questionnaire was distributed to 740 hospitals in Japan with pediatric beds, and 208 (28.1%) of these hospitals responded. The total instances of compounding numbered 14,864 (9.6% of the total pediatric oral prescriptions) and comprised 266 active pharmaceutical ingredients (APIs), one-third of which (98 APIs) were compounded even though flexible dosage forms were available. The three most frequently compounded drugs were dantrolene sodium capsules (1152 prescriptions), ramelteon tablets (726 prescriptions), and hydrocortisone tablets (652 prescriptions), all of which were prescribed and administered in powder form. Although compounding of medications frequently varied by the patients’ age, steroids such as prednisolone, dexamethasone, and hydrocortisone were commonly compounded in all age groups. To ensure the quality and safety of these compounded medications, developing a standard protocol for compounding methods is urgently needed in Japan.

Control of oral absorption of nutritional supplement using lipid-based formulations (LBFs): Application to the poorly water-soluble ingredient

Among various formulations for oral use, lipid-based formulation (LBF) has been expected as a promising technology to improve the absorption of poorly water-soluble compounds. In the current study, three types of LBFs were tested for their effects on the extent, rate and variability of oral absorption of sesamin. Olive oil (type 1), type 3A-MC (medium-chain lipids) and type 3A-LC (long-chain lipids) formulations were prepared to test the intestinal absorption of sesamin in rats. Both type 3A formulations showed a rapid absorption of sesamin with minimized inter-individual variability compared to Olive oil formulation. Extent of absorption was in the order of 3A-LC > Olive oil > 3A-MC ≫ powder suspension. It was revealed that 3A-LC formulation kept the high solubilization capacity even under the lipid-digestive condition giving a high concentration of free sesamin. In the dog study, 3A-LC formulation also showed a high and less-variable absorption of sesamin, although the absorption was subjected to the effect of food intake. In conclusion, the extent, rate and variability of oral absorption of sesamin could be controlled by using different types of LBFs, indicating the possibility to develop better oral products of supplements using appropriate formulations.

Design of self-dispersible microsponge containing cyclosporine through wet milling and drop freeze-drying processes to improve dissolution behavior

Cyclosporine (Cyc) is an immunosuppressant used to treat psoriasis and atopic dermatitis and mainly commercialized as a soft capsule due to its poorly water-soluble characteristics. The authors attempted to develop the solid pharmaceutical formulations for oral use (granules, tablet) with improved solubility of Cyc. In this research, a manufacturing method of spherical granules containing nano-sized Cyc particles was newly developed by using the combination between wet milling and drop freeze-drying (DFD) technique. Cyc nanosuspension prepared through wet-milling process was poured dropwise into liquid nitrogen, and the resultant spherical ice grains were freeze-dried to prepare granules with around 300 μm in size. The granules prepared through these sequential processes were identified as porous spherical granules having submicron Cyc particles embedded in water-soluble fiber network structure of additives. When they were placed in aqueous phase, water would immediately penetrate into the matrix of granules through the pores. Subsequently, Cyc particles were spontaneously dispersed into the media as soon as matrix base was dissolved, resulting in the reconstitution of nano-suspension. As a result, the resultant DFD granule, named microsponge, had fast dissolution behavior of more than 80% within 10 min in aqueous phase. The dissolution rate of Cyc from the microsponge strongly depended on the size of embedded Cyc particles, demonstrating that the wet nano-milling must be indispensable process to prepare the microsponge.

Labrasol® is an efficacious intestinal permeation enhancer across rat intestine: Ex vivo and in vivo rat studies

Labrasol® ALF (Labrasol®), is a non-ionic surfactant excipient primarily used as a solubilising agent. It was investigated here as an intestinal permeation enhancer in isolated rat colonic mucosae in Ussing chamber and in rat in situ intestinal instillations. Labrasol® comprises mono-, di- and triglycerides and mono- and di- fatty acid esters of polyethylene glycol (PEG)-8 and free PEG-8, with caprylic (C8)- and capric acid (C10) as the main fatty acids. Source components of Labrasol® as well as Labrasol® modified with either C8 or C10 as the sole fatty acid components were also tested to determine which element of Labrasol® was responsible for its permeability-enhancing properties. Labrasol® (4, 8 mg/mL) enhanced the transport of the paracellular markers, [14C] mannitol, FITC-dextran 4000, and FITC-insulin across colonic mucosae. The enhancement was non-damaging, transient, and molecular weight-dependent. The PEG ester fraction of Labrasol® also had enhancing properties. When insulin was administered with Labrasol® in instillations, it had a relative bioavailability of 7% in jejunum and 12% in colon. C8– and C10 versions of Labrasol® and the PEG ester fraction also induced similar bioavailability values in jejunal instillations: 6, 5 and 7% respectively. Inhibition of lipases in instillations did not reduce the efficacy of Labrasol®, suggesting that its mechanism as a PE is not simply due to liberated medium chain fatty acids. Labrasol® acts as an efficacious intestinal permeation enhancer and has potential for use in oral formulations of macromolecules and BCS Class III molecules.

Sex Differences in the Prevalent Use of Oral Formulations of Cholinesterase Inhibitors in Older Adults with Dementia.

Cholinesterase inhibitors (ChEIs) are one of only two drug therapies available to manage cognitive decline in dementia. Given sex-specific differences in medication access and effects, it is important to understand how ChEIs are used by women and men. The objective of this study was to provide contemporary sex-stratified evidence on patterns of ChEI use by community-dwelling older adults with dementia to inform opportunities to optimize drug prescribing. We conducted a population-based cross-sectional study examining ChEI use in older adults with dementia in Ontario, Canada. We identified all community-dwelling individuals aged 66 years and older with a pre-existing diagnosis of dementia as of 1 April, 2016. We examined the prevalence of ChEI use among women and men separately, and explored the association between ChEI use and age, sex, income status, geographic location of residence, use of palliative care services, comorbidity, and polypharmacy. Concurrent use of drugs known to impair cognition (including antipsychotics, benzodiazepines, and medications with strong anticholinergic properties) was separately assessed among women and men using multivariable analyses and prevalence risk ratios. Of 74,799 women and 52,231 men living with dementia in the community, nearly 30% currently were using a ChEI (29.3% women, 28.6% men). Close to 70% of users were receiving the target therapeutic dose. Compared to men, women were less often taking the target therapeutic dose (67.8% women vs. 71.6% men, p < 0.001). Over 20% of users also were using drugs known to impair cognition, while being treated for cognitive decline using ChEIs. Compared to men, women were more often concurrently using drugs known to impair cognition (23.9% women vs. 21.8% men, p < 0.001). This is one of the first studies of ChEI use to account for important sex differences. The results remind clinicians and researchers that patterns of ChEI therapy use differ by sex, as women were less likely to receive target therapeutic doses and more vulnerable to potentially problematic polypharmacy than men.

Cytotoxicity screening of emulsifiers for pulmonary application of lipid nanoparticles

IntroductionThe pulmonary route is a non-invasive administration route that receives growing attention. The challenge for formulation development of orally inhaled formulations is, however, the limited number of approved excipients. Lipid nanoparticles are desired drug delivery systems for inhalation because lipids are biocompatible. However, addition of emulsifiers to stabilize the formulation may cause toxic effects. Alveolar epithelial cells and alveolar macrophages are the main cell types that get in contact with inhaled formulations in the deep lung. The different cell types are supposed to differ in the extent of particle uptake. Kolliphor RH40, Poloxamer 188, and Tween 80 are approved for use in oral formulations and widely used in the academic field for manufacturing of lipid nanoparticles. However, little is known about their pulmonary toxicity. MethodsCytotoxicity of Kolliphor RH40, Poloxamer 188, and Tween 80 was studied by integration into solid lipid nanoparticles loaded with itraconazole as model drug. Cytotoxicity of the formulations was assessed in human alveolar epithelial cells and human and murine macrophages and correlated to cell uptake. ResultsThe tested emulsifiers showed overall low cytotoxicity with less pronounced adverse effects in human cells than in murine macrophages. Cellular uptake of Poloxamer 188 containing lipid nanoparticles was decreased in macrophages, while uptake of lipid nanoparticles with the other emulsifiers was similar in epithelial cells and phagocytes. ConclusionThe tested emulsifiers appear suitable for use in pulmonary applications. Due to larger cell size and lower proliferation rate human cells showed lower cytotoxicity than the murine cells. Being human cells, they appear more suitable for the screening of adverse effects in human lungs.

Alternative Pharmaceutical Formulation for Oral Administration of Rifampicin.

Tuberculosis (TB) is considered an emergency global public health, mainly due to the TB-HIV co-infection, bacillus dormancy stage, and emergence of resistant strains. In addition, the therapeutic toxicity and its pharmacokinetic interactions with other drugs may influence treatment non-compliance, low serum concentration of drugs, and, consequently, treatment failure. Strategies using nanotechnology represent a new tool for the therapy, since they are effective delivery systems due to the possibility of solubilization of hydrophobic compounds, enable the production of formulations for oral use, and, in addition, increase bioavailability of drugs. This study aimed to develop a nanoemulsion (NE) containing rifampicin (RIF-NE) and evaluate its in vitro antimycobacterial activity using Resazurin Microtiter Assay against three Mycobacterium tuberculosis strains: two susceptible and a multidrug-resistant. Using the hot solvent diffusion method associated with phase inversion technique was possible to develop a liquid formulation containing 500 μg/mL rifampicin (RIF), which is a hydrophobic compound, of average size 25 nm. The results showed that the minimum inhibitory concentration of the encapsulated RIF was equal to the free form of RIF, indicating that the process of production of NEs did not affect the activity of the compound. Thus, RIF-NE could be a promising alternative for oral administration of RIF, being considered a child-friendly pharmaceutical formulation. Its application could avoid the administration of unknown and/or non-ideal concentrations, being functional in the regimes of prevention and treatment of TB and, in addition, in the fight against drug resistance.

Availability of pediatric-evaluated formulations in Serbia.

OBJECTIVES:The aim of this study is to analyze the availability and coverage by health insurance reimbursement of pediatric formulations labeled for children up to the age of 12 in Serbia. To provide good insight in general availability of pediatric medicines, results were compared with the World Health Organization's (WHO) “Model List of Essential Medicines for Children” and with published evidence.MATERIALS AND METHODS:Sources of information about medicines are the Summary of Product Characteristics, National Health Insurance Fund (NHIF) Drug Lists, WHO Model Lists of Essential Medicines for Children, and Serbia's official drug registry (2013).RESULTS:Out of total number of medicines in Serbia, only 49% (496) were available for children. Of all available drugs for children, 66% were with license and majority were parenteral formulation (57%), followed by drugs for local use (28%) and formulations for oral use (23%). The lowest availability of medicines was for children 0–27 days. From the total number of licensed medicines for children up to 12 years old, NHIF covers 64% of drugs. The availability of the WHO essential medicines for children in Serbia was 51%, from which 92% were licensed for pediatric use.CONCLUSIONS:Our results demonstrated the alarming lack of pediatric suitable formulations in Serbia. Significant differences in the availability of drugs suitable for children exist worldwide. From global health point of view, the differences in the access to children formulations should, therefore, be of the highest priority.

THe quantitative determination of sildenafil in human plasma by high performance liquid chromatography - mass spectrometry (lc-ms/ms)

Purpose. For the study of pharmacokinetics of sildenafil oral spray “Tegrum”, developed by pharmaceutical company “Microkhim” (Rubezhnoe, Ukraine) with the aim to improve the pharmacokinetic characteristics of existing solid formulations for oral use it was worked out and validated a rapid, simple and specific method of quantitative determination of sildenafil concentration in human plasma using internal standard labeled with 8 deuterium atoms - sildenafil-d8.Methods. Sildenafil was extracted from plasma by the liquid-liquid extraction, and quantitatively determined in supernatant by means of а high performance liquid chromatography - tandem mass spectrometry method (HPLC-MS/MS). Separation of components was performed using the chromatographic column Kinetex 2.6u C18, 50 x 4.6 mm, 2.6 μm (Phenomenex) at 45˚C at isocratic elution mode and mobile phase, that consisted of 2 mM aqueous ammonium acetate solution (pH 5,45 ± 0,05) and acetonitrile (10/90, vol./vol.); flow rate equaled to 0.4 ml/min. Ionization of sildenafil and sildenafil-d8 was performed in the positive electrospray mode (ESI, Positive). Multi reactions monitoring (MRM) mode was used for selected daughter and parent ions detection with the following settings of the mass spectrometer: m/z 475,20/283,20 and 483.20/283.20 for sildenafil and sildenafil-d8 respectively.Results. The method described above was validated in the linear range 10,00-400,00 ng/mL of sildenafil with a correlation coefficient (r2) 0,99764 and demonstrated reliable accuracy and reproducibility of results.Conclusions. Utilization of elaborated method of fast direct liquid - liquid sildenafil extraction from the blood plasma with simultaneous proteins precipitation, avoiding commonly used supernatant evaporation and subsequent restoration of dry residue at preanalytical stage allowed to achieve target sensitivity of determination and reduced the analysis runtime. Usage of the deuterated internal standard (sildenafil-d8) at analytical stage gave an opportunity to reduce the limit of quantification, to achieve high sensitivity and specificity, as well as suppress matrix effect. Rather high analytical characteristics of the method proposed allow its application in routine bioanalysis during pharmacokinetic studies.

Molecular dynamics simulations in drug delivery research: Calcium chelation of G3.5 PAMAM dendrimers.

Poly(amido amine) (PAMAM) dendrimers have been considered as possible delivery systems for anticancer drugs. One potential advantage of these carriers would be their use in oral formulations, which will require absorption in the intestinal lumen. This may require the opening of tight junctions which may be enabled by reducing the Ca2+ concentration in the intestinal lumen, which has been shown as an absorption mechanism for EDTA (ethylenediaminetetraacetic acid). Using molecular dynamics simulations, we show that the G3.5 PAMAM dendrimers are able to chelate Ca2+ at similar proportions to EDTA, providing support to the hypothesis that oral formulations of PAMAM dendrimers could use this high chelating efficiency as a potential mechanism for permeating the tight junctions of the intestines if other formulation barriers could be overcome.

AVAILABILITY OF PAEDIATRIC-EVALUATED FORMULATIONS IN SERBIA

Background/ObjectiveA lack of appropriately evaluated medicines for paediatric population is a major problem as it often leads to inadequate treatment of children. The aim of this study was to investigate the availability of paediatric formulations labelled for children up to the age of 12 years old in Serbia in 2013, as well as the availability of paediatric medicines reimbursed by the Republic Health Insurance Fund (RFZO). The availability of paediatric formulations in Serbia is also compared with the ‘Model List of Essential Medicines for Children’ by World Health Organization's (WHO).MethodsSources of information about medicines were: the Summary of Product Characteristics (SmPc), RFZO Drug Lists, WHO Model Lists of Essential Medicines for Children, and Serbia's official drug registry, editions 2013.ResultsIn Serbia only 49% (496) of INN drugs were suitable for children of which only 66% were licensed for paediatric use. Majority of licensed drugs were parenteral formulations, 57%, followed by drugs for local use, 28%, and formulations for oral use, 23%. The lowest availability of medicines was for children 0–27 days old. From the total number of licensed medicines for children up to 12 years old, the Republic Fund for Health Insurance covers 64% of drugs and from each therapeutic group at least one medicine is reimbursed by fund. The availability of WHO essential medicines for children in Serbia was 51%, from which 92% were licensed for paediatric use.ConclusionOur study showed that from already unsatisfactory number of available drugs for children only 66% is licensed. Limited availability of paediatric medicines for all ages of this population and for a broad range of therapeutic areas still represents a cause for concern in our country.

Association of hormone therapy and incident gout: population-based case-control study.

This study aims to assess the odds of developing incident gout in association with the use of postmenopausal estrogen-progestogen therapy, according to type, timing, duration, and route of administration of estrogen-progestogen therapy. We conducted a retrospective population-based case-control analysis using the United Kingdom-based Clinical Practice Research Datalink. We identified women (aged 45 y or older) who had a first-time diagnosis of gout recorded between 1990 and 2010. We matched one female control with each case on age, general practice, calendar time, and years of active history in the database. We used multivariate conditional logistic regression to calculate odds ratios (ORs) with 95% CIs (adjusted for confounders). The adjusted OR for gout with current use of oral formulations of opposed estrogens (estrogen-progestogen) was 0.69 (95% CI, 0.56-0.86) compared with never use. Current use was associated with a decreased OR for gout in women without renal failure (adjusted OR, 0.71; 95% CI, 0.57-0.87) and hypertension (adjusted OR, 0.62; 95% CI, 0.44-0.87) compared with never use. Tibolone was associated with a decreased OR for gout (adjusted OR, 0.77; 95% CI, 0.63-0.95) compared with never use. Estrogens alone did not alter the OR for gout. Current use of oral opposed estrogens, but not unopposed estrogens, is associated with a decreased OR for incident gout in women without renal failure and is more pronounced in women with hypertension. Use of tibolone is associated with a decreased OR for incident gout. The decreased OR for gout may be related to the progestogen component rather than the estrogen component.

Efficacies of Antimicrobial Conservants of Various Nonsterile Medicines for Oral Use

The efficacies of the antimicrobial conservants in a number of nonsterile medicinal formulations for oral use as syrups and solutions were evaluated, i.e., Klarisens® syrup 1 mg/ml, El’kar® solution for oral use, 300 mg/ml, Lasolvan® syrup 15 mg/5 ml, and others. The quality of seven study samples containing conservants such as benzoic acid, methylparaben, propylparaben, sodium benzoate, and ethanol complied with the requirements of General Pharmacopeia Monograph OFS 42-0069-07 “Determination of the efficacy of antimicrobial conservants in medicines”. The results of the studies reported here were obtained using a modified deep plate inoculation method recommended by the State Pharmacopeia of the Russian Federation XII edition for determination of the microbiological purity of medicines. The modified deep plate method has potential for use as a supplementary method, and inclusion in the next edition of the State Pharmacopeia of the Russian Federation is recommended.

Use of oral formulations of fentanyl for breakthrough cancer pain.

Use of oral formulations of fentanyl for breakthrough cancer pain.

Donor-Derived Strongyloides stercoralis Infections in Renal Transplant Recipients

Donor-derived Strongyloides stercoralis infection occurs rarely after transplantation, and the risk factors are not well understood. We present cases of two renal allograft recipients who developed Strongyloides hyperinfection syndrome after receipt of organs from a common deceased donor who received high-dose steroids as part of a preconditioning regimen. The two renal transplant patients who developed Strongyloides hyperinfection syndrome are reported in case study format with review of the literature. Microscopic examination of stool from one renal transplant patient and of tracheal and gastric aspirates from the other transplant patient revealed evidence of S. stercoralis larvae. Retrospective testing of serum from the deceased donor for Strongyloides antibodies by enzyme-linked immunosorbent assay was positive at 11.7 U/mL (Centers for Disease Control reference >1.7 U/mL positive). One patient was treated successfully with oral ivermectin. The other patient also had complete resolution of strongyloidiasis, but required a course of parenteral ivermectin because of malabsorption from severe gastrointestinal strongyloidiasis. These case studies provide some of the best evidence of transmission of S. stercoralis by renal transplantation. Because of the high risk of hyperinfection syndrome and its associated morbidity and mortality, high-risk donors and recipients should be screened for Strongyloides infection, so that appropriate treatment can be initiated before the development of disease. This study indicates that parenteral ivermectin can be used safely and effectively in patients in whom severe malabsorption would preclude the effective use of oral formulation. These cases also suggest that reconsideration should be given for the safety of steroids in donor-preconditioning regimens.

A possible pH-controlled drug delivery system based on a derivative of the polysaccharide scleroglucan.

Four carboxylated derivatives of scleroglucan have been obtained by oxidation, to different extents, of the glucopyranose side chains of the natural polysaccharide. The diffusion of model molecules through aqueous solutions of these new products was measured at various pH values. The reversible pH induced sol-gel transition of some of the polyelectrolyte solutions tested effects a remarkable variation in the diffusion rate of the permeating species; in this sense the most interesting polysaccharide appears to be the product with 70% oxidized glucopyranose moieties. The behaviour of scleroglucan and its derivatives has been compared with that of carboxymethylcellulose and the mechanism involved in drug permeation and release discussed. The possible application of one of the new products in controlled release formulations for oral use is also reported.