1,721,021 research outputs found
Role of novel drug delivery systems in bioavailability enhancement: at a glance
No full textNovel drug delivery systems (NDDS) are one of the most strategies which enable to overcome the problems related to drug bioavailability. It is the rate and extent to which a drug becomes available to the target tissue after its administration. Most of the new drugs used today have poor bioavailability and are required to be administered at higher doses because only a small fraction of the administered dose is absorbed in the systemic circulation and able to reach the target site. This results in the wastage of major amount of drug and lead to adverse effects. Pharmaceutical technology mainly focuses on enhancing the solubility and permeability of drugs with lower bioavailability. Nanotechnology is the concept used in NDDS that enables a weight reduction of drug particles accompanied by an increase in stability and improved functionality. Various approaches such as nanosuspensions, liposomes, niosomes, nanoemulsions, cubosomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), cyclodextrins, phytosome etc., are used for the enhancement of bioavailability. The present review focuses on the different approaches used for bioavailability enhancement along with their advantages and disadvantage
The selective targeting of cancer cells by using Pheroid® as a drug delivery system
No full textPheroid® is a drug delivery system with possible use in the
treatment of chronic diseases such as cancer and that enhances the
efficacy of the treatment of chronic diseases [1]. Current cancer
treatment is non-selective, has serious long-term side-effects and
sometimes is life-threatening [2]. Certain drug delivery systems can
be used to improve the safety, stability and efficiency of cancer therapy [3]. Various types of Pheroid® can be formulated and
custom-made for different applications [1]. Pheroid® has the
potential to be formulated to specifically target cancer cells and to
improve the bio- availability and efficacy of anti-cancer drugs.
Pheroid® will be formulated with folic acid and transferrin
covalently attached to the fatty acids that will be incorporated in
the Pheroid®. These ligands are specifically chosen as the receptors
for these ligands are overexpressed in certain cancer types. Mass
spectrometry and NMR spectrometry will be used to confirm
attachment. Cisplatin will be used as active ingredient that will be
encapsulated in the Pheroid®. These formulations will be characterized and stability tests will be performed to determine the stability of
the formulations. In vitro study will be performed with breast (MCF7) and lung (A549) cancer cell lines and will include cytotoxicity
assays and cellular uptake assays to confirm selectivity. In vivo
efficacy of the formulations will be performed on xenografts models
of MCF-7 and A549 cell lines. A pharmacokinetic study and a tissue
bio-distribution study will be performed to determine the selectivity
of the Pheroid® formulations against cancer cells. The following
results are anticipated for this study: Successfully attachment of
ligands to fatty acids incorporated in Pheroid®; Selective targeting of
cancer cells by Pheroid®; Accumulation of Pheroid® in tumor
environment; Improve efficacy and safety of cisplatin treatment.
This study will contribute to knowledge in the cancer research field
and selective targeting of cancer cells by Pheroid® drug delivery
system. We anticipate to patent the targeting of this technology and
the use of it in cancer therap
In vitro determination of the preclinical safety of Pheroid® doxorubicin formulations using patch clamp assays
No full textOne of the most active, widely used and well-known drugs in
breast cancer chemotherapy, doxorubicin (DOX), is an anthracycline
ring antibiotic derived from the bacteria Streptomyces peucetius. Its
clinical use is however, hampered by dangerous side effects like
cumulative dose-dependent cardiotoxicity (leading to myocardiopathy). Consequently, DOX often has a narrow therapeutic
index and compromised therapeutic potential. DOX-induced myocardiopathy is a fatal ailment and with the development of heart
failure the mortality rate is approximately 50%. Acute DOX
cardiotoxicity is characterized by electrocardiogram irregularities
like prolongation of the interval between the Q and T waves. With
the absence of effective treatment for DOX-induced myocardiopathy,
preventive measures include limiting the lifetime cumulative dose of
Basic Live/dead differentiation
Sensitivity Sensitivity
80% Cohort n = 20 60% Cohort n = 20
100% (S + C+) n = 11 82% (S + C+) n = 11
56% (S-C+) n = 9 33% (S-C+) n = 9
Specificity Specificity
84% Cohort n = 68 88% Cohort n = 68
87% (S–C–) n = 60 90% (S–C–) n =
63% (S + C-) n = 8 75% (S + C–) n = 8
Abstracts 3
DOX to b450 mg/m2
, use of continuous slow infusion in place of
normal infusion protocols, replacement of DOX with anthracycline
analogues, and use of different drug delivery carriers. The aim of this
project is to develop a functionalized Pheroid® drug delivery carrier,
with extravesicular targeting ligands specifically directing delivery of
DOX to breast cancer cells which will increase therapeutic efficacy
and reduce toxicity to healthy cells. In vitro patch clamp assays will
be conducted to evaluate the effect of entrapping DOX in Pheroid®
formulations on acute QT prolongation. We would analyze the IKr
(rapid component of the delayed rectifier current) and IKs (second
component of the delayed rectifier current) of cultured HEK (human
embryonic kidney)-293 cells permanently transfected with the
human ether-a-go-go related gene (hERG) and KCNQ1/KCNE1 genes,
respectively, using the whole-cell configuration of the patch clamp
technique. Functionalized Pheroids, with ligands specific to receptors
overexpressed on breast cancer cells, as drug delivery vehicles for
DOX could improve drug accumulation at the cancerous tissue
through passive and active targeting and minimize acute
cardiotoxicity of DOX. From this study we would be able to
determine in vitro the preclinical safety with respect to the
torsadogenic potential of formulations of DOX in Pheroid
Rapid cell lysis and DNA capture in a lysis microreactor
No full textIn clinical diagnostics, the detection and identification of bacterial organisms based on the analysis of their nucleic acids require cell lysis and DNA extraction from clinical samples. A lysis microreactor (LMR) has been developed to perform these tasks with high efficiency and in processing times of approximately 5–10 min. In this paper we report on (1) the kinetics of lysis, (2) the efficiency of DNA capture onto a strip that is inserted into the reactor and (3) application to the detection of Mycobacterium tuberculosis from clinical sputum samples. The LMR has a capacity of 2 ml and it is fitted with an impeller and temperature control. A polystyrene strip, inserted into the LMR at the start of the lysis process, captures the lysed ssDNA. Following a brief overview of the kinetics of lysis, the computational fluid dynamics results of the LMR are shown and a model of the DNA capture is presented. The application to clinical samples and controls demonstrates that this is a promising technology for fast turn-around times and sensitive diagnostics
Synthesis and evaluation of hybrid drugs for a potential HIV/AIDS-malaria combination therapy
No full textMalaria and HIV are among the most important global health problems of our time and together are responsible for approximately 3 million deaths annually. These two diseases overlap in many regions of the world including sub-Saharan Africa, Southeast Asia and South America, leading to a higher risk of co-infection. In this study, we generated and characterized hybrid molecules to target Plasmodium falciparum and HIV simultaneously for a potential HIV/malaria combination therapy. Hybrid molecules were synthesized by the covalent fusion of azidothymidine (AZT) with dihydroartemisinin (DHA), a tetraoxane or a 4-aminoquinoline derivative; and the small library was tested for antiviral and antimalarial activity. Our data suggests that compound 7 is the most potent molecule in vitro, with antiplasmodial activity comparable to that of DHA (IC50 = 26 nM, SI >3000), a moderate activity against HIV (IC50 = 2.9 μM; SI >35) and not toxic to HeLa cells at concentrations used in the assay (CC50 >100 μM). Pharmacokinetics studies further revealed that compound 7 is metabolically unstable and is cleaved via O-dealkylation. These studies account for the lack of in vivo efficacy of compound 7 against the CQ-sensitive Plasmodium berghei N strain in mice, when administered orally at 20 mg/kg
Nano- and Pheroid technologies for development of foliar iron fertilizers and iron biofortification of soybean grown in South Africa
No full textBackground
Foliar iron (Fe) fertilization of crops may increase Fe concentrations in edible portions of plants and improve yield in soils with low available Fe. However, the role of foliar Fe fertilization in increasing seed Fe has not been studied in soybeans (Glycine max). In this study, the Pheroid® nutrient delivery technology was combined with FeSO4 or nanostructured FePO4 to develop potential new Fe foliar fertilizers. Eight different treatments including different combinations of FeSO4 and Pheroids were foliarly applied on field-grown soybeans in Northern Cape province in South Africa to investigate their influence on seed nutrient composition and yield.
Results
Confocal and optical microscopy images indicate that FeSO4 or FePO4 was not entrapped in the Pheroids but formed separate precipitates. The average seed Fe of the non-treated plants was 56 ± 3 mg kg−1, and none of the treatments (including the positive controls, FeSO4 and FeSO4 with citrate) significantly increased seed Fe over the control. There was also no significant change in yield or seed Zn, P, protein, or phytic acid. Thus, Pheroids as well as FeSO4 are not suitable as delivery system for Fe to soybean seeds due to Pheroid incompatibility with FeSO4 and poor dispersibility of FePO4.
Conclusions
Because none of the Fe treatments (including positive controls) affected seed Fe concentrations, foliar Fe application may not be effective to increase seed Fe in crops such as soybean that already have high native F
Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites
Get PDFS-adenosyl-L-methionine decarboxylase (AdoMetDC) in the polyamine biosynthesis pathway has been
identified as a suitable drug target in Plasmodium falciparum parasites, which causes the most lethal form
of malaria. Derivatives of an irreversible inhibitor of this enzyme, 50-{[(Z)-4-amino-2-butenyl]methylamino}-
50-deoxyadenosine (MDL73811), have been developed with improved pharmacokinetic profiles
and activity against related parasites, Trypanosoma brucei. Here, these derivatives were assayed for
inhibition of AdoMetDC from P. falciparum parasites and the methylated derivative, 8-methyl-50-{[(Z)-
4-aminobut-2-enyl]methylamino}-50-deoxyadenosine (Genz-644131) was shown to be the most active.
The in vitro efficacy of Genz-644131 was markedly increased by nanoencapsulation in immunoliposomes,
which specifically targeted intraerythrocytic P. falciparum parasitesDepartment of Science and Technology through the South
African Malaria Initiative, the University of Pretoria, the South African
National Research Foundation and by grant BIO2011-25039
from the Ministerio de Economía y Competitividad, Spain, which
included FEDER funds, and 2009SGR-760 from the Generalitat de
Catalunya, Spai
The Deep Genome Project
Get PDFIn vivo research is critical to the functional dissection of multi-organ systems and whole organism physiology, and the laboratory mouse remains a quintessential animal model for studying mammalian, especially human, pathobiology. Enabled by technological innovations in genome sequencing, mutagenesis and genome editing, phenotype analyses, and bioinformatics, in vivo analysis of gene function and dysfunction in the mouse has delivered new understanding of the mechanisms of disease and accelerated medical advances. However, many significant hurdles have limited the elucidation of mechanisms underlying both rare and complex, multifactorial diseases, leaving significant gaps in our scientific knowledge. Future progress in developing a functionally annotated genome map depends upon studies in model organisms, not least the mouse. Further, recent advances in genetic manipulation and in vivo, in vitro, and in silico phenotyping technologies in the mouse make annotation of the vast majority of functional elements within the mammalian genome feasible. The implementation of a Deep Genome Project—to deliver the functional biological annotation of all human orthologous genomic elements in mice—is an essential and executable strategy to transform our understanding of genetic and genomic variation in human health and disease that will catalyze delivery of the promised benefits of genomic medicine to children and adults around the world
Pulmonary delivery of anti-tubercular drugs using ligand anchored pH sensitive liposomes for the treatment of pulmonary tuberculosis
No full textBackground: Mycobacterium tuberculosis (M. TB) remains the prime cause of bacterial mortality and morbidity world-wide. Therefore, effective delivery and targeting of drug to the cellular tropics is essentially required to generate significant results for tuberculosis treatment. The aim of the present study was to develop and characterize ligand anchored pH sensitive liposomes (TPSL) as dry powder inhaler for the targeted delivery of drugs in the target site i.e. lungs.
Method: Ligand anchored PSL (TPSL) was prepared by thin film hydration for the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-α-D mannopyranoside (Man) as surface functionalized ligand and characterized using different parameters.
Results: It was observed that size of the ligand anchored liposomes (TPSL) was slightly more than the non-ligand anchored liposomes (PSL). Drug release was studied at different pH for 24 hrs and it was observed that liposomes exhibited slow release at alkaline pH (58-64%) as compared to macrophage pH (81-87%) where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand anchored liposomes as compared to its counterpart. In vivo study showed that maximum drug accumulation was achieved in the lung by delivering drug using ligand anchored PSL as compared to conventional PSL.
Conclusion: It was concluded that ligand anchored pH sensitive liposome is one of the promising systems for the targeted drug therapy in pulmonary tuberculosi
A model of isoniazid treatment of tuberculosis
No full textA mathematical model is presented of the growth and death of bacilli in a granuloma. The granuloma is treated with isoniazid (INH), a drug that inhibits the synthesis of mycolic acids (MA). Since MA is an essential component of cell walls, the organisms fail to reach maturity if deficient in MA. Cell wall turnover is a well-known feature of bacteria, at the exterior surface material sloughs off to foil attacks by hosts or other organisms, simultaneously synthesizing products for new cell wall assembly. Thus cell wall thickness is maintained in a dynamic equilibrium (Doyle et al., 1988). Presumably cell death is a result of loss in cell wall due to autolysis in combination with stinted replenishing. The mathematical model presented here uses differential equations to predict the effects of intracellular INH on cell wall thickness and cell viability. This analysis purposely distinguishes intracellular INH concentration from the concentration in the plasma. The concentration in the plasma depends only on the dosing. The intracellular INH concentration, however, depends on diffusion through the cell walls of the bacteria. This paper addresses the complex interactions between intracellular INH, cell wall thickness, and the rate of cell wall synthesisTechnology Innovation
Agency (TIA) of South Afric
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