Roger New - Academia.edu (original) (raw)
Papers by Roger New
Parasitology, Dec 1, 1981
SUMMARYTreatment of cutaneous leishmaniasis by antimonial compounds when administered by various ... more SUMMARYTreatment of cutaneous leishmaniasis by antimonial compounds when administered by various routes to mice infected with Leishmania major or L. mexicana amazonensis is enhanced, relative to the free drug, by entrapment of these compounds within liposomes. The efficacy of the liposome treatment is dependent on the time and route of administration, and upon the phospholipid composition of the liposomes themselves. Drug-loaded liposomes administered intravenously (i.v.) are more effective at reducing the growth of a cutaneous lesion if they are administered after the nodule has begun to develop, rather than at the time of inoculation of the parasites. In contrast to the i.v. route, liposomes administered subcutaneously (s.c.) at the inoculation site are only effective if given at the time of infection.
Advanced Drug Delivery Reviews, Apr 1, 1997
Association of peptides with oil carriers can improve the delivery of these molecules by affordin... more Association of peptides with oil carriers can improve the delivery of these molecules by affording protection against intestinal proteases, improving stability in the presence of gut surfactants and altering cell permeability and lymphatic secretion. Intestinal delivery of calcitonin using an oil-based formulation is illustrated in the pig, and a new technology (‘Macrosol’) is described in which hydrophilic molecules are solubilised
Journal of Biomaterials Science-polymer Edition, 1995
Segmented polyurethane ureas with different hard segment content and composition were synthesized... more Segmented polyurethane ureas with different hard segment content and composition were synthesized using 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols. Using polyols with different molecular weights, it was possible to synthesize polyurethane ureas with either: (i) a constant ratio of urethane to urea bonds; (ii) a constant urethane content; or (iii) a constant urea content. Bulk properties were assessed by dynamic mechanical analysis. Surface properties were estimated by contact angle measurements and streaming potential measurements. Haemocompatibility was evaluated in vitro by measuring the adsorption of human serum albumin (HSA) and fibrinogen (Fg), the adhesion of human peripheral blood lymphocytes (PBL), and the presence of activated platelets on the biomaterial surfaces. Enzyme immuno assays (EIA) have been specially developed for this purpose for the detection of antibody-recognizable plasma proteins and platelet surface membrane proteins. No simple correlation between chemical structure of the polymers and surface properties was found. Parameters of haemocompatibility correlated more closely with hard segment content and chemical composition than with the surface characteristics of the polymers. Adsorption of plasma proteins, adhesion of lymphocytes and the adhesion/activation of platelets were found to increase with increasing hard segment content of the polyurethane ureas. However, the monoclonal-antibody recognisable fibrinogen and the platelet activation were nearly constant with increasing hard segment content, if the urea content was kept constant.
Toxicon, 1985
OTHMAR ZUMHUEHL, DALE. IDDON rI'o whom reprint requests should be sent .
Annals of Tropical Medicine and Parasitology, 1994
Concentrations of albendazole were measured, by high-pressure liquid chromatography, in 19 patien... more Concentrations of albendazole were measured, by high-pressure liquid chromatography, in 19 patients being treated for cystic echinococcosis. All of the patients were given three 4-week courses of albendazole (20 mg/kg/day), separated by 10-day-long drug-free intervals. Seven patients also received three courses of cimetidine (10 mg/kg/day). Concentrations of albendazole sulphoxide (ABZSX) were significantly higher in samples of bile and hydatid cyst fluid from the patients receiving albendazole and cimetidine than in those from patients receiving albendazole alone (P < 0.05). The therapeutic benefit of the combined drug treatment, which was well-tolerated, was more than that with albendazole alone.
Diabetes, Obesity and Metabolism, 2010
Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) ... more Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Methods: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m 2 , haemoglobin A 1c (HbA 1c) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Results: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280-330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC 0-6 h (910 ± 270 vs. 472 ± 245 pmol h/L; 950 ± 446 vs. 433 ± 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA 1c , weight and triglycerides were observed. Conclusions: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations.
Transactions of The Royal Society of Tropical Medicine and Hygiene, May 1, 1994
Human echinococcosis is highly endemic in northwestern China; the main treatment is by surgery. I... more Human echinococcosis is highly endemic in northwestern China; the main treatment is by surgery. In this naner. we renort the results of chemotheranv with albendazole (ABZ). 15-20 rng/kg/d orallv. for 30 d with $t&&ls of i0 d between treatments for 3-&courses. For multi-brgan cystic ecl&oFoccosis ICE) and alveolar echinococcosis (AE), patients were given 12-18 courses of ABZ. Patients were divided into 4 groups: (i) ABZ surgery group, albendazole with surgery for 21 CE cases: (ii) non-ABZ surgery group, 80 CE cases treated by surgery alone; (iii) ABZ CE group, albendazole treatment alone in 58 CE cases, and (iv) ABZ AE group, 14 AE patients treated by albendazole and surgical intervention and 5 AE patients treated by albendazole alone. Twenty-seven of 34 (79.4%) cysts in group (i) patients showed increased necrotic changes and decreased viability of the cysts compared to group (ii). However, 10 of 84 (11.9%) cysts in group (ii) patients showed spontaneous evidence of necrosis at surgery. In group (iii), ABZ treatment alone was successful in 14 (24.1%)1, resulted in improvement in 29 (50%) and had no effect in 15 (25.9%) patients. Seven cases in group (iv) improved, with diminished size of lesions which were non-viable. The remaining 7 cases in group (iv) showed evidence of cyst viability at surgery; 2 could not be saved after a further 15 courses of albendazole. Of the five AE patients in group (iv) who received only ABZ, one improved, 2 stabilized, one deteriorated and one died. Albendazole chemotherapy, while not completely effective, has an important role in treatment of both cystic and alveolar echinococcosis.
Toxicon, 1985
Use of liposomes for protective immunisation in sheep against Echis rnrinatus snake venom. Toxico... more Use of liposomes for protective immunisation in sheep against Echis rnrinatus snake venom. Toxicon 23, 921-923, 1983 .-Nigerian Echis carlnatus vrnom incorporated into sphingomyeGntholesterol liposomes stabilized with osmium tetroxide produced a rapid, sustained and protective immune response whrn injected i .v. into sheep. The response was similar to that reported earlier in mia. The implications of the findings are discussed in relation to the production of cheaper and more effective antivrnoms. The possible use of immunostimulants for increasing the protective effect of antisera raised using this method are also considered .
Molecular and Biochemical Parasitology, May 1, 1984
This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony glu... more This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony gluconate after i.v. administration to mice infected with Leishmania donovani. It was demonstrated that entrapment within liposomes greatly altered the kinetics of uptake of the drug. We were also able to show that liposomes composed of sphingomyelin, stearylamine and cholesterol were marginally better than any other preparation in delivering entrapped drug to liver and spleen. X-ray microanalytical studies on the uptake of liposomes by Kupffer cells infected with L. donovani have indicated that internalised liposomes probably fuse with parasitophorous vacuoles, transferring their contents into the immediate locality of the leishmanial parasites. It is proposed that this is the way in which liposome entrapped antileishmanial agents have an enhanced therapeutic effect over free drug therapy.
Antiviral Research, May 1, 2010
Induction of mucosal immunity through oral immunization is an effective way to control influenza ... more Induction of mucosal immunity through oral immunization is an effective way to control influenza infection. In this study, baculovirus displaying influenza hemagglutinin was encapsulated within a reverse micelle structure of phosphatidylcholine and delivered into the gastrointestinal tract of mice to study its efficacy as an oral vaccine against cross-clade H5N1 infection. Mice vaccinated with encapsulated baculovirus displaying HA (En-BacHA) showed significantly enhanced HA specific serum IgG and mucosal IgA antibodies, and higher hemagglutination inhibition (HI) titers, when compared to its non-encapsulated form (BacHA). Estimation of serum neutralizing antibodies also indicated that En-BacHA formulation was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1, clade 4.0 and clade 8.0). Further, mice vaccinated with En-BacHA alone were able to confer 100% protection against 5MLD50 of HPAI heterologous H5N1 strain (clade 1). Inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant in the vaccine formulation did not show any significant effect in both systemic and mucosal immune responses. Oral delivery of encapsulated recombinant H5 HA expressed on baculovirus surface is an effective way to prime the immune system against H5N1 infection in mice and will have no biosafety concerns associated with their production or administration.
Parasitology, Aug 1, 1996
Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparatio... more Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparation in which this normally insoluble anti-hydatid drug is well solublilized in aqueous media. The high entrapment efficiency observed (75-87 %) and the stability of the formulation make this a promising delivery vehicle for improved chemotherapy with albendazole. In particular, the high degree of association with phospholipid may give rise to increased oral bioavailability. Oral administration of albendazole in liposomes led to increased concentration and/or altered metabolism of albendazole sulphoxide (ABZSX) in liver and/or plasma in non-infected Wistar rats. Results from experiments using cotton rats (Sigmodon hispidus) infected with metacestodes of Echinococcus multilocularis show that entrapment within liposomes clearly increases the uptake of albendazole via the oral route. This was reflected by increased levels of albendazole and the two major metabolites in plasma, liver and cyst homogenate when a dose of liposomal albendazole (35 mg/kg) was given orally compared to free albendazole at 50 mg/kg. There was a 75-94 % reduction in biomass of the metacestode and a significant increase in survival time for the animals treated with liposome entrapped albendazole. A clear difference in distribution of albendazole and its metabolites in the liver and the metacestode tissues in the presence of cimetidine indicated that the latter has a profound effect on the metabolism of albendazole. There appeared to be a synergistic interaction between albendazole and cimetidine, since the metabolism of albendazole was markedly altered in the combined cimetidine/ liposome-albendazole group, and higher therapeutic effect was observed. These findings indicate potential both for improvement of treatment of larval E. multilocularis infection and for reduction of albendazole dose levels.
Journal of Antimicrobial Chemotherapy, 1981
Introduction Liposome therapy for visceral leishmaniasis has been described using antimonial comp... more Introduction Liposome therapy for visceral leishmaniasis has been described using antimonial compounds by several independent laboratories (Alving et al, 1978; Black, Watson & Ward, 1977; New et al., 1978), and owes its success to the fact that both liposomes and the ...
British Journal of Clinical Pharmacology, Jun 1, 1993
Diabetes, Obesity and Metabolism
AimTo compare the pharmacodynamic properties of different doses of regular human insulin administ... more AimTo compare the pharmacodynamic properties of different doses of regular human insulin administered in capsule form twice daily in a randomised twelve‐week open‐label study.MethodsA total of 100 individuals (48 males, 52 females) with type 2 diabetes on metformin completed the study according to the protocol. The mean (SD) age was 48.5 (6.7) years, body mass index 25.7 (2.8) kg/m2 and HbA1c 8.10% (0.65%). Subjects randomized upon admission were assigned to one of three groups receiving formulated regular insulin at dose levels of 75 iu BD, 150 iu insulin BD, or 300 iu BD, all in enteric‐coated capsules. The primary and secondary endpoints were change from baseline in HbA1c and fasting plasma glucose (FPG), respectively.ResultsThe study met its primary clinical endpoint of a decrease in HbA1c of 0.5% or higher (least square mean decrease 0.52%; P = .004, median decrease 0.6%) in the dose group receiving 150 iu BD. In a subset of this population, with starting HbA1c values of 9% to ...
Although strong binding interactions between protein receptor and ligand do not require the parti... more Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis.
We describe a new method of combinatorial screening in which building blocks, instead of being li... more We describe a new method of combinatorial screening in which building blocks, instead of being linked together chemically, are placed on the surface of nanoparticles. Two-or three-dimensional structures form on the surface of these particles through the close approach of different building blocks, with sufficient flexibility to be able to adapt and interact with putative binding sites in biological systems. The particles assemble without the need for formation of chemical bonds, so libraries comprised of many structures can be prepared rapidly, with large quantities of material available for testing. Screening methods can include solid and solution-phase binding assays, or tissue culture models, for example looking for structures which can change the behaviour of cells in a disease-modifying manner.
Phospholipids Handbook, 2018
Parasitology, Dec 1, 1981
SUMMARYTreatment of cutaneous leishmaniasis by antimonial compounds when administered by various ... more SUMMARYTreatment of cutaneous leishmaniasis by antimonial compounds when administered by various routes to mice infected with Leishmania major or L. mexicana amazonensis is enhanced, relative to the free drug, by entrapment of these compounds within liposomes. The efficacy of the liposome treatment is dependent on the time and route of administration, and upon the phospholipid composition of the liposomes themselves. Drug-loaded liposomes administered intravenously (i.v.) are more effective at reducing the growth of a cutaneous lesion if they are administered after the nodule has begun to develop, rather than at the time of inoculation of the parasites. In contrast to the i.v. route, liposomes administered subcutaneously (s.c.) at the inoculation site are only effective if given at the time of infection.
Advanced Drug Delivery Reviews, Apr 1, 1997
Association of peptides with oil carriers can improve the delivery of these molecules by affordin... more Association of peptides with oil carriers can improve the delivery of these molecules by affording protection against intestinal proteases, improving stability in the presence of gut surfactants and altering cell permeability and lymphatic secretion. Intestinal delivery of calcitonin using an oil-based formulation is illustrated in the pig, and a new technology (‘Macrosol’) is described in which hydrophilic molecules are solubilised
Journal of Biomaterials Science-polymer Edition, 1995
Segmented polyurethane ureas with different hard segment content and composition were synthesized... more Segmented polyurethane ureas with different hard segment content and composition were synthesized using 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols. Using polyols with different molecular weights, it was possible to synthesize polyurethane ureas with either: (i) a constant ratio of urethane to urea bonds; (ii) a constant urethane content; or (iii) a constant urea content. Bulk properties were assessed by dynamic mechanical analysis. Surface properties were estimated by contact angle measurements and streaming potential measurements. Haemocompatibility was evaluated in vitro by measuring the adsorption of human serum albumin (HSA) and fibrinogen (Fg), the adhesion of human peripheral blood lymphocytes (PBL), and the presence of activated platelets on the biomaterial surfaces. Enzyme immuno assays (EIA) have been specially developed for this purpose for the detection of antibody-recognizable plasma proteins and platelet surface membrane proteins. No simple correlation between chemical structure of the polymers and surface properties was found. Parameters of haemocompatibility correlated more closely with hard segment content and chemical composition than with the surface characteristics of the polymers. Adsorption of plasma proteins, adhesion of lymphocytes and the adhesion/activation of platelets were found to increase with increasing hard segment content of the polyurethane ureas. However, the monoclonal-antibody recognisable fibrinogen and the platelet activation were nearly constant with increasing hard segment content, if the urea content was kept constant.
Toxicon, 1985
OTHMAR ZUMHUEHL, DALE. IDDON rI'o whom reprint requests should be sent .
Annals of Tropical Medicine and Parasitology, 1994
Concentrations of albendazole were measured, by high-pressure liquid chromatography, in 19 patien... more Concentrations of albendazole were measured, by high-pressure liquid chromatography, in 19 patients being treated for cystic echinococcosis. All of the patients were given three 4-week courses of albendazole (20 mg/kg/day), separated by 10-day-long drug-free intervals. Seven patients also received three courses of cimetidine (10 mg/kg/day). Concentrations of albendazole sulphoxide (ABZSX) were significantly higher in samples of bile and hydatid cyst fluid from the patients receiving albendazole and cimetidine than in those from patients receiving albendazole alone (P < 0.05). The therapeutic benefit of the combined drug treatment, which was well-tolerated, was more than that with albendazole alone.
Diabetes, Obesity and Metabolism, 2010
Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) ... more Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Methods: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m 2 , haemoglobin A 1c (HbA 1c) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Results: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280-330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC 0-6 h (910 ± 270 vs. 472 ± 245 pmol h/L; 950 ± 446 vs. 433 ± 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA 1c , weight and triglycerides were observed. Conclusions: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations.
Transactions of The Royal Society of Tropical Medicine and Hygiene, May 1, 1994
Human echinococcosis is highly endemic in northwestern China; the main treatment is by surgery. I... more Human echinococcosis is highly endemic in northwestern China; the main treatment is by surgery. In this naner. we renort the results of chemotheranv with albendazole (ABZ). 15-20 rng/kg/d orallv. for 30 d with $t&&ls of i0 d between treatments for 3-&courses. For multi-brgan cystic ecl&oFoccosis ICE) and alveolar echinococcosis (AE), patients were given 12-18 courses of ABZ. Patients were divided into 4 groups: (i) ABZ surgery group, albendazole with surgery for 21 CE cases: (ii) non-ABZ surgery group, 80 CE cases treated by surgery alone; (iii) ABZ CE group, albendazole treatment alone in 58 CE cases, and (iv) ABZ AE group, 14 AE patients treated by albendazole and surgical intervention and 5 AE patients treated by albendazole alone. Twenty-seven of 34 (79.4%) cysts in group (i) patients showed increased necrotic changes and decreased viability of the cysts compared to group (ii). However, 10 of 84 (11.9%) cysts in group (ii) patients showed spontaneous evidence of necrosis at surgery. In group (iii), ABZ treatment alone was successful in 14 (24.1%)1, resulted in improvement in 29 (50%) and had no effect in 15 (25.9%) patients. Seven cases in group (iv) improved, with diminished size of lesions which were non-viable. The remaining 7 cases in group (iv) showed evidence of cyst viability at surgery; 2 could not be saved after a further 15 courses of albendazole. Of the five AE patients in group (iv) who received only ABZ, one improved, 2 stabilized, one deteriorated and one died. Albendazole chemotherapy, while not completely effective, has an important role in treatment of both cystic and alveolar echinococcosis.
Toxicon, 1985
Use of liposomes for protective immunisation in sheep against Echis rnrinatus snake venom. Toxico... more Use of liposomes for protective immunisation in sheep against Echis rnrinatus snake venom. Toxicon 23, 921-923, 1983 .-Nigerian Echis carlnatus vrnom incorporated into sphingomyeGntholesterol liposomes stabilized with osmium tetroxide produced a rapid, sustained and protective immune response whrn injected i .v. into sheep. The response was similar to that reported earlier in mia. The implications of the findings are discussed in relation to the production of cheaper and more effective antivrnoms. The possible use of immunostimulants for increasing the protective effect of antisera raised using this method are also considered .
Molecular and Biochemical Parasitology, May 1, 1984
This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony glu... more This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony gluconate after i.v. administration to mice infected with Leishmania donovani. It was demonstrated that entrapment within liposomes greatly altered the kinetics of uptake of the drug. We were also able to show that liposomes composed of sphingomyelin, stearylamine and cholesterol were marginally better than any other preparation in delivering entrapped drug to liver and spleen. X-ray microanalytical studies on the uptake of liposomes by Kupffer cells infected with L. donovani have indicated that internalised liposomes probably fuse with parasitophorous vacuoles, transferring their contents into the immediate locality of the leishmanial parasites. It is proposed that this is the way in which liposome entrapped antileishmanial agents have an enhanced therapeutic effect over free drug therapy.
Antiviral Research, May 1, 2010
Induction of mucosal immunity through oral immunization is an effective way to control influenza ... more Induction of mucosal immunity through oral immunization is an effective way to control influenza infection. In this study, baculovirus displaying influenza hemagglutinin was encapsulated within a reverse micelle structure of phosphatidylcholine and delivered into the gastrointestinal tract of mice to study its efficacy as an oral vaccine against cross-clade H5N1 infection. Mice vaccinated with encapsulated baculovirus displaying HA (En-BacHA) showed significantly enhanced HA specific serum IgG and mucosal IgA antibodies, and higher hemagglutination inhibition (HI) titers, when compared to its non-encapsulated form (BacHA). Estimation of serum neutralizing antibodies also indicated that En-BacHA formulation was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1, clade 4.0 and clade 8.0). Further, mice vaccinated with En-BacHA alone were able to confer 100% protection against 5MLD50 of HPAI heterologous H5N1 strain (clade 1). Inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant in the vaccine formulation did not show any significant effect in both systemic and mucosal immune responses. Oral delivery of encapsulated recombinant H5 HA expressed on baculovirus surface is an effective way to prime the immune system against H5N1 infection in mice and will have no biosafety concerns associated with their production or administration.
Parasitology, Aug 1, 1996
Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparatio... more Encapsulation of the benzimidazole albendazole in multilamellar liposomes results in a preparation in which this normally insoluble anti-hydatid drug is well solublilized in aqueous media. The high entrapment efficiency observed (75-87 %) and the stability of the formulation make this a promising delivery vehicle for improved chemotherapy with albendazole. In particular, the high degree of association with phospholipid may give rise to increased oral bioavailability. Oral administration of albendazole in liposomes led to increased concentration and/or altered metabolism of albendazole sulphoxide (ABZSX) in liver and/or plasma in non-infected Wistar rats. Results from experiments using cotton rats (Sigmodon hispidus) infected with metacestodes of Echinococcus multilocularis show that entrapment within liposomes clearly increases the uptake of albendazole via the oral route. This was reflected by increased levels of albendazole and the two major metabolites in plasma, liver and cyst homogenate when a dose of liposomal albendazole (35 mg/kg) was given orally compared to free albendazole at 50 mg/kg. There was a 75-94 % reduction in biomass of the metacestode and a significant increase in survival time for the animals treated with liposome entrapped albendazole. A clear difference in distribution of albendazole and its metabolites in the liver and the metacestode tissues in the presence of cimetidine indicated that the latter has a profound effect on the metabolism of albendazole. There appeared to be a synergistic interaction between albendazole and cimetidine, since the metabolism of albendazole was markedly altered in the combined cimetidine/ liposome-albendazole group, and higher therapeutic effect was observed. These findings indicate potential both for improvement of treatment of larval E. multilocularis infection and for reduction of albendazole dose levels.
Journal of Antimicrobial Chemotherapy, 1981
Introduction Liposome therapy for visceral leishmaniasis has been described using antimonial comp... more Introduction Liposome therapy for visceral leishmaniasis has been described using antimonial compounds by several independent laboratories (Alving et al, 1978; Black, Watson & Ward, 1977; New et al., 1978), and owes its success to the fact that both liposomes and the ...
British Journal of Clinical Pharmacology, Jun 1, 1993
Diabetes, Obesity and Metabolism
AimTo compare the pharmacodynamic properties of different doses of regular human insulin administ... more AimTo compare the pharmacodynamic properties of different doses of regular human insulin administered in capsule form twice daily in a randomised twelve‐week open‐label study.MethodsA total of 100 individuals (48 males, 52 females) with type 2 diabetes on metformin completed the study according to the protocol. The mean (SD) age was 48.5 (6.7) years, body mass index 25.7 (2.8) kg/m2 and HbA1c 8.10% (0.65%). Subjects randomized upon admission were assigned to one of three groups receiving formulated regular insulin at dose levels of 75 iu BD, 150 iu insulin BD, or 300 iu BD, all in enteric‐coated capsules. The primary and secondary endpoints were change from baseline in HbA1c and fasting plasma glucose (FPG), respectively.ResultsThe study met its primary clinical endpoint of a decrease in HbA1c of 0.5% or higher (least square mean decrease 0.52%; P = .004, median decrease 0.6%) in the dose group receiving 150 iu BD. In a subset of this population, with starting HbA1c values of 9% to ...
Although strong binding interactions between protein receptor and ligand do not require the parti... more Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis.
We describe a new method of combinatorial screening in which building blocks, instead of being li... more We describe a new method of combinatorial screening in which building blocks, instead of being linked together chemically, are placed on the surface of nanoparticles. Two-or three-dimensional structures form on the surface of these particles through the close approach of different building blocks, with sufficient flexibility to be able to adapt and interact with putative binding sites in biological systems. The particles assemble without the need for formation of chemical bonds, so libraries comprised of many structures can be prepared rapidly, with large quantities of material available for testing. Screening methods can include solid and solution-phase binding assays, or tissue culture models, for example looking for structures which can change the behaviour of cells in a disease-modifying manner.
Phospholipids Handbook, 2018