7,960 research outputs found
Development and evaluation of a reconstitutable dry suspension containing isoniazid for flexible pediatric dosing
No full textTuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is neglected globally as evidenced by treatment and clinical care schemes, mostly extrapolated from studies in adults. The objective of this study was to formulate and evaluate a reconstitutable dry suspension (RDS) containing isoniazid, a first-line anti-tubercular agent used in the treatment and prevention of TB infection in both children and adults. The RDS formulation was prepared by direct dispersion emulsification of an aqueous-lipid particulate interphase coupled with lyophilization and dry milling. The RDS appeared as a cream-white free-flowing powder with a semi-crystalline and microparticulate nature. Isoniazid release was characterized with an initial burst up to 5 minutes followed by a cumulative release of 67.88% ± 1.88% (pH 1.2), 60.18% ± 3.33% (pH 6.8), and 49.36% ± 2.83% (pH 7.4) over 2 h. An extended release at pH 7.4 and 100% drug liberation was achieved within 300 min. The generated release profile best fitted the zero order kinetics (R2 = 0.976). RDS was re-dispersible and remained stable in the dried and reconstituted states over 4 months and 11 days respectively, under common storage condition
Functionalization of PLGA nanoparticles with 1,3-β-glucan enhances the intracellular pharmacokinetics of rifampicin in macrophages
No full textPurpose
Mycobacterium tuberculosis which causes tuberculosis, is primarily resident within macrophages. 1,3-β-glucan has been proposed as a ligand to target drug loaded nanoparticles (NPs) to macrophages. In this study we characterized the intracellular pharmacokinetics of the anti-tubercular drug rifampicin delivered by 1,3-β-glucan functionalized PLGA NPs (Glu-PLGA). We hypothesized that Glu-PLGA NPs would be taken up at a faster rate than PLGA NPs, and consequently deliver higher amounts of rifampicin into the macrophages.
Methods
Carbodiimide chemistry was employed to conjugate 1,3-β-glucan and rhodamine to PLGA. Rifampicin loaded PLGA and Glu-PLGA NPs as well as rhodamine functionalized PLGA and Glu-PLGA NPs were synthesized using an emulsion solvent evaporation technique. Intracellular pharmacokinetics of rifampicin and NPs were evaluated in THP-1 derived macrophages. A pharmacokinetic model was developed to describe uptake, and modelling was performed using ADAPT 5 software.
Results
The NPs increased the rate of uptake of rifampicin by a factor of 17 and 62 in case of PLGA and Glu-PLGA, respectively. Expulsion of NPs from the macrophages was also observed, which was 3 fold greater for Glu-PLGA NPs than for PLGA NPs. However, the ratio of uptake to expulsion was similar for both NPs. After 24 h, the amount of rifampicin delivered by the PLGA and Glu-PLGA NPs was similar. The NPs resulted in at least a 10-fold increase in the uptake of rifampicin.
Conclusions
Functionalization of PLGA NPs with 1,3-β-glucan resulted in faster uptake of rifampicin into macrophages. These NPs may be useful to achieve rapid intracellular eradication of Mycobacterium tuberculosi
Co-administration of African potato and cisplatin for treating breast and prostate cancers using a Pheroid® delivery system
No full textThe cancer burden is increasing worldwide and is expected tobecome the most important barrier to increasing life expectancy 21stcentury. Low- and middle-income countries are expected to showthe biggest increase in incidence. Cisplatin is a frequently usedchemotherapy, however, challenges like drug resistance and sideeffects have yet to be overcome. A promising solution to thisproblem is the co- administration of cisplatin with other compounds.Many cancer patients in sub-Saharan countries co-administer herbaland prescription drugs. African potato (AP) is a popular choice for itsnegligible side effects and immune-boosting properties. One problemassociated with orally administered drug is poor bioavailability. ThePheroid® delivery system has shown to improve drug bioavailabilityand efficacy. No studies have been done on the interaction between AP and cisplatin, hence, this study aims to formulate a combinationof AP and cisplatin in Pheroids® and evaluate its anticancerproperties. Cytotoxicity of AP and cisplatin will be testedin vitroagainst breast (MCF-7) and prostate (PC-3) cancer cell lines todetermine the combination (CI) and dose reduction index of AP withcisplatin. Pheroids® will be examined for their optimal formulation.Anticancer activity of Pheroid® formulations will be tested throughvarious assays. For the pharmacokinetic study, Sprague- Dawley ratswill be used due to the volume of the blood samples required. Ratswill be administered with cisplatin, unformulated AP-cisplatin orPheroid® formulated AP-cisplatin (N= 10). For the efficacy study,nude mice that will be used as the models have already beenestablished. Animals will be implanted with either PC-3 or MCF-7cells. Once tumor volume has reached≥150 mm3 they will be treatedwith cisplatin, unformulated AP-cisplatin, Pheroid® formulated AP-cisplatin or empty Pheroids® (N= 10). AP and cisplatin have asimilar mode of action, hence synergistic activity whenco-administered is expected. As a result, lower concentrations ofcisplatin are expected to yield potent activity compared to individualadministration, for both Pheroid® formulations and free drugformulation
Development and validation of an LC-MS/MS method for the quantification of goserelin in a Pheroid (R) formulation, in simulated intestinal fluid
No full textThe purpose of this reported study was to develop and validate an LC-MS/MS method for the quantification of goserelin in a Pheroid (R) formulation simulated intestinal fluid. Biopharmaceuticals are formulated in drug delivery systems to improve their gastrointestinal stability. Goserelin, a peptide drug was formulated in Pheroid (R) delivery system and its gastrointestinal stability assessed using simulated intestinal fluid, which required an assay to determine the varying amounts of goserelin remaining after a specific time. Several extraction methods and solvents investigated to extract goserelin from complex matrix led to either poor recovery, peak shape or high background interference. A rapid gradient reversed-phase method coupled to tandem mass spectrometry detection was optimized for the separation and quantification of the extracted peptide. A simple, reproducible and good recovery extraction procedure for goserelin quantification was achieved through simultaneous acetonitrile protein precipitation and water-saturated n-butanol liquid-liquid extraction with water dilution. The method was found to be rapid, specific, precise and accurate, and successfully applied to determine goserelin remaining content in a simulated intestinal fluid, with potential use in other lipid-based formulation evaluated in simulated intestinal fluids. (C) 2019 Elsevier B.V. All rights reserve
The fabrication and characterization of a PLGA nanoparticle–Pheroid® combined drug delivery system
No full textThe combination of polymeric nanoparticles (NPs) as a core and lipid vesicles as a shell has emerged to be a robust and promising drug delivery strategy. This study explores the development of a novel combined delivery system where poly d,l, lactic-co-glycolic acid (PLGA) NPs are entrapped within Pheroid® drug delivery system. The solid NPs were combined with the Pheroid® vesicles using two different methods: pre-mix and post-mix. The surface properties of the PLGA NPs were altered through the inclusion (pos-NPs) and exclusion (neg-NPs) of chitosan (CT) and polyethylene glycol (PEG), to evaluate their interaction with the Pheroid® Vesicles. The average particle size of the novel NP–Pheroid® combined system ranged from approximately 1990–2450 nm while the zeta potential (ZP) ranged from −18 to −30 mV, measured using dynamic light scattering (DLS) and electrophoretic velocity techniques, respectively. The NP/Pheroid® mixing ratio experiment indicated that a maximum of 2.5% (w/v) NPs can be optimally added to the Pheroid® vesicles without compromising the structure and the stability of the NP–Pheroid® combined system. Visual analysis of this system was done through transmission electron microscopy (TEM), cryogenic (cryo) TEM and confocal laser scanning microscopy (CLSM) techniques to obtain adequate information of this novel combined drug delivery system which includes the localization of the PLGA NPs with the Pheroid® vesicle
Trip account
No full textTrip account - AMs, 15 pp.
“I am attempting to give you some account of a recent vacation trip which we were privileged to enjoy - Rose, Mother and I…” As the account of the trip to view the eclipse is unsigned, we can’t say for sure but as the author states “Rose, Mother and I” one could logically assume that the author is a sibling of T. Rose Curtis
ROSE POLY and ME A Memoir
No full textAuthor discusses his time as an engineering student and football player (1955-59), and then football coach, track coach, athletic director, instructor and then assistant professor of civil engineering at Rose Polytechnic Institute (now Rose-Hulman Institute of Technology) (1962-64). As a football player in 1958, he led the nation in scoring with 168 points in 8 games. Sixty-two years later, the 168 points continues to be the record for points in a season by an Indiana college football player. His 21.0 points per game were the national record for thirty years (1958-88) until broken by Barry Sanders of Oklahoma State. In 1957 and 1958, the Rose Poly football team won fifteen games in a row over two seasons while the defense held opponents to 5.4 points per game. In 1958, the team led the NCAA Division II in defense holding opponents to 95.8 yards per game and a total of 31 points (3.9 points per game). As the football coach, he rescued the team from a disastrous previous year in which the team lost all of its games and scored only six points. The author concludes with his afterthoughts on his alma mater after a career of more than 60 years in engineering education.https://scholar.rose-hulman.edu/alum_pub/1003/thumbnail.jp
Establishment and characterization of a murine HSV-2 model for the evaluation of a novel microbicide
No full textHerpes simplex virus −2 (HSV-2) is a serious global epidemic
with an estimated 400 million people infected and about 20 million
cases reported annually. The prevalence in South Africa is at 31% in
females aged 15–29 years old. Microbicides are self-administered
topical agents which provide women-controlled protection against
sexually transmitted infections (STIs). There is an urgent need for
microbicides which not only inhibit HSV-2 and other STIs but also
reduce the risk of HIV contraction. There is a lack of in vivo models to
evaluate the safety and efficacy of novel microbicides, hence this
study aims to provide an HSV-2 challenge model which can be used
to evaluate the safety and efficacy of novel microbicides. Safety
assessment of the microbicide was done at 500 μg/mL in male and
female Balb/c mice (n = 8) and were inoculated intrarectally and
intravaginally respectively. Rectal and vaginal tissue samples were
collected 2 h post-inoculation for histology. For model establishment,
1×06 PFU of the HSV-2 strain G virus was used. In the efficacy of the
microbicide, male and female mice (n = 10) were inoculated with
10 μl microbicide 10 min before being inoculated with the virus and
the control group were inoculated with sterile phosphate buffered
saline. The experiments were conducted in a BSL3 lab. The mice were
monitored for infection twice a day over 10 days. Histological
analysis showed that the microbicide was safe to use as there were
no signs of tissue damage. The amounts of virus used was sufficient
to induce a definite infection within 8 days. Application of the novel
microbicide delayed mortality rate in the challenge group up to day
19 in both male and female groups compared to day 8 in the control
group. Balb/c mice are highly susceptible to the HSV-2 virus and are
an appropriate model for microbicide studie
In vivo evaluation of acute intravenous toxicity of a [Ga-68]Ga-PSMA-11-microemulsion
No full textMicroemulsions (MEs) are reported to improve the efficacy of a drug, minimise side effects and toxicity of the encapsulated compound. MEs are hypothesized to aid in making the encapsulated compound, which has been incorporated within the ME, safe in vivo due to reduced side effects and toxicity to the kidneys and other non-target organs. This study aimed to contribute to knowledge on the toxicity of the ME delivery system and ME containing [68Ga]Ga-PSMA-11 with specific reference to intravenous tail vein administration. ME and [68Ga]Ga-PSMA-11-ME were synthesized by homogenisation under high temperature and a dose of 150 μl per mouse was administered intravenously in 10 healthy male BALB/c mice. The mice were monitored and evaluated for 14 days for clinical signs, mortality, body weights, and gross necropsy findings. The mice were euthanized after the respective 14-day period followed by isolation of respective organs and blood samples. Blood test results included assessment of alanine transaminase, aspartate transaminase, total protein, urea, creatinine and serum lipid levels. There were no abnormal changes observed in the body weight, coat condition, respiration, mobility and behaviour of any of the mice during the study. The survival rate was 10/10 mice (100%) after 14 days. None of the treatment groups showed any treatment related toxicity to either ME or [68Ga]Ga-PSMA-11-ME. Blood testing showed that liver and kidney function was in the normal range in both mice groups. This treatment regimen of the administered ME and [68Ga]Ga-PSMA-11-ME concentration caused no acute toxicity to small rodents but further investigations are required in larger animal models to justify the safety of [68Ga]Ga-PSMA-11-ME injections into human
Development of an LC-MS/MS method for the quantification of goserelin from Pheroid® formulation
No full textThe oral route is for many reasons the most common route of
drug administration, however, due to gastrointestinal (GI) tract
enzymatic stability issues, peptide drugs are administered parenterally. Goserelin is an anticancer peptide drug which has been recently
encapsulated in the Pheroid® delivery system to enhance its GI
enzymatic stability. In vitro stability of Pheroid®-goserelin formulation was therefore evaluated in simulated intestinal fluids. An assay
was required to extract and quantify goserelin from Pheroid®
formulation in the presence of simulated intestinal fluids. However,
a literature survey revealed no analytical method available for such
task. Hence, in this study, novel LC-MS/MS assay was developed and
validated for goserelin quantification in formulation and intestinal
fluids. Pheroid®-goserelin formulation was incubated in simulated
gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) for 120
min after which the enzymatic reaction was stopped with acetonitrile in the ratio of 1:3 (v/v). Goserelin was extracted from Pheroid®-
goserelin formulation in the simulated intestinal fluids using a
protein precipitation method prior to liquid-liquid extraction with
water-saturated n-butanol and water. A gradient reverse-phase
method with tandem mass spectrometry detection was optimized
for the separation and quantification of the extracted goserelin.
Several extraction methods and solvents investigated to extract
goserelin from the lipids and proteins mixture led to either poor
recovery or poor peak shape. A simple, reproducible and highrecovery extraction procedure for goserelin quantification was
achieved using both protein precipitation method and liquid-liquid
extraction with water-saturated n-butanol and water. Moreover,
chromatographic separation and tandem mass spectrometry detection for goserelin and its internal standard were achieved within a
total analysis time of 2 min. The challenge for this study was to
develop a method to extract goserelin from a matrix comprising lipid
and proteins. The stopping reaction reagent (acetonitrile) simultaneously functioned as the protein precipitation solvent, whilst the
lipids were successfully extracted using liquid-liquid extraction with
water-saturated n-butanol and water. This novel assay was found to
be specific, rapid, precise and accurate and could be applied to the
goserelin in vitro preclinical stability stud
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