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Expert Opinion on Drug Delivery Nov 2016One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious... (Review)
Review
One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, sub-optimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered: This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion: The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored.
Topics: Albumins; Animals; Cattle; Drug Carriers; Drug Delivery Systems; Humans; Ligands; Nanoparticles; Nanostructures; Nanotechnology; Pharmaceutical Preparations; Rats
PubMed: 27216915
DOI: 10.1080/17425247.2016.1193149 -
British Journal of Clinical Pharmacology Jun 2019A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy...
AIMS
A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery.
METHODS
An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1 day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individual-specific covariates were added in sequence.
RESULTS
The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k ), but it also increased losses of fluid from the kinetic system (k ). The balance between k and k maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k ) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates.
CONCLUSIONS
There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers.
Topics: Abdomen; Adult; Albumins; Female; Fluid Shifts; Fluid Therapy; Humans; Infusions, Intravenous; Male; Models, Biological; Plasma Substitutes; Postoperative Care; Sweden; Treatment Outcome; Young Adult
PubMed: 30756411
DOI: 10.1111/bcp.13897 -
Acta Biomaterialia Sep 2022Therapeutic benefits of curcumin for inflammatory diseases have been demonstrated. However, curcumin's potential as a clinical therapeutic has been hindered due to its...
Therapeutic benefits of curcumin for inflammatory diseases have been demonstrated. However, curcumin's potential as a clinical therapeutic has been hindered due to its low solubility and stability in vivo. We hypothesized that a hybrid curcumin carrier that incorporates albumin-binding and extracellular vesicle (EV) encapsulation could effectively address the current challenges of curcumin delivery. We further postulated that using dissolvable microneedle arrays (dMNAs) for local delivery of curcumin-albumin-EVs (CA-EVs) could effectively control skin inflammation in vivo. Mild sonication was used to encapsulate curcumin and albumin into EVs, and the resulting CA-EVs were integrated into tip-loaded dMNAs. In vitro and in vivo studies were performed to assess the stability, cellular uptake, and anti-inflammatory bioactivity of dMNA-delivered CA-EVs. Curcumin in CA-EVs exhibited at least five-fold higher stability in vitro than naïve curcumin or curcumin-EVs without albumin. Incorporating CA-EVs into dMNAs did not alter their cellular uptake or anti-inflammatory bioactivity. The dMNA embedded CA-EVs retained their bioactivity when stored at room temperature for at least 12 months. In rat and mice models, dMNA delivered CA-EVs suppressed and significantly reduced lipopolysaccharide and Imiquimod-triggered inflammation. We conclude that dMNA delivery of CA-EVs has the potential to become an effective local-delivery strategy for inflammatory skin diseases. STATEMENT OF SIGNIFICANCE: We introduce and evaluate a skin-targeted delivery system for curcumin that synergistically combines albumin association, extracellular-vesicle encapsulation, and dissolvable microneedle arrays (dMNAs) . In vitro, curcumin-albumin encapsulated extracellular vesicles (CA-EVs) inhibit and reverse the LPS-triggered expression of inflammatory transcription factor NF-κB. The integration of CA-EVs into dMNAs does not affect them physically or functionally. Importantly, dMNAs extend EV storage stability for at least 12 months at room temperature with minimal loss in their bioactivity. We demonstrate that dMNA delivered CA-EVs effectively block and reverse skin inflammation in vivo in mouse and rat models.
Topics: Albumins; Animals; Anti-Inflammatory Agents; Curcumin; Extracellular Vesicles; Inflammation; Mice; Rats
PubMed: 35809788
DOI: 10.1016/j.actbio.2022.06.046 -
European Journal of Nuclear Medicine... May 2022
Topics: Albumins; Fibroblasts; Gelatinases; Humans; Radioisotopes; Serine Endopeptidases
PubMed: 35332379
DOI: 10.1007/s00259-022-05766-0 -
MBio Jun 2021Albumin is abundant in serum but is also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic...
Albumin is abundant in serum but is also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic pathogens encounter albumin during commensalism and when causing infections. Considering the ubiquitous presence of albumin, we investigated its role in the pathogenesis of infections with the model human fungal pathogen, Candida albicans. Albumin was introduced in various models that mimic different stages of systemic or mucosal candidiasis, where it reduced the ability of C. albicans to damage host cells. The amphipathic toxin candidalysin mediates necrotic host cell damage induced by C. albicans. Using cellular and biophysical assays, we determined that albumin functions by neutralizing candidalysin through hydrophobic interactions. We discovered that albumin, similarly, can neutralize a variety of fungal (α-amanitin), bacterial (streptolysin O and staurosporin), and insect (melittin) hydrophobic toxins. These data suggest albumin as a defense mechanism against toxins, which can play a role in the pathogenesis of microbial infections. Albumin is the most abundant serum protein in humans. During inflammation, serum albumin levels decrease drastically, and low albumin levels are associated with poor patient outcome. Thus, albumin may have specific functions during infection. Here, we describe the ability of albumin to neutralize hydrophobic microbial toxins. We show that albumin can protect against damage induced by the pathogenic yeast C. albicans by neutralizing its cytolytic toxin candidalysin. These findings suggest that albumin is a toxin-neutralizing protein that may play a role during infections with toxin-producing microorganisms.
Topics: Albumins; Candida albicans; Candidiasis; Cell Line; Cells, Cultured; Female; Fungal Proteins; HT29 Cells; Host-Pathogen Interactions; Humans; Hydrophobic and Hydrophilic Interactions; Mucous Membrane; Vagina; Virulence Factors
PubMed: 34154403
DOI: 10.1128/mBio.00531-21 -
Annual Review of Biochemistry Jun 2017Lipids are produced site-specifically in cells and then distributed nonrandomly among membranes via vesicular and nonvesicular trafficking mechanisms. The latter... (Review)
Review
Lipids are produced site-specifically in cells and then distributed nonrandomly among membranes via vesicular and nonvesicular trafficking mechanisms. The latter involves soluble amphitropic proteins extracting specific lipids from source membranes to function as molecular solubilizers that envelope their insoluble cargo before transporting it to destination sites. Lipid-binding and lipid transfer structural motifs range from multi-β-strand barrels, to β-sheet cups and baskets covered by α-helical lids, to multi-α-helical bundles and layers. Here, we focus on how α-helical proteins use amphipathic helical layering and bundling to form modular lipid-binding compartments and discuss the functional consequences. Preformed compartments generally rely on intramolecular disulfide bridging to maintain conformation (e.g., albumins, nonspecific lipid transfer proteins, saposins, nematode polyprotein allergens/antigens). Insights into nonpreformed hydrophobic compartments that expand and adapt to accommodate a lipid occupant are few and provided mostly by the three-layer, α-helical ligand-binding domain of nuclear receptors. The simple but elegant and nearly ubiquitous two-layer, α-helical glycolipid transfer protein (GLTP)-fold now further advances understanding.
Topics: Albumins; Allergens; Animals; Antigens; Binding Sites; Biological Transport; Carrier Proteins; Gene Expression; Humans; Lipid Metabolism; Lipids; Models, Molecular; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Domains
PubMed: 28375742
DOI: 10.1146/annurev-biochem-061516-044445 -
Annals of Hepatology Dec 2021Introduction and objectives It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with... (Meta-Analysis)
Meta-Analysis
Introduction and objectives It has been suggested that albumin administration could alter the natural history of cirrhosis, and also, that long-term treatment with albumin might be associated with improvement in survival, control of ascites, reduction in the incidence bacterial infections, renal dysfunction, hepatic encephalopathy (HE) and hyponatremia, as well as reduction in length of hospitalization in patients with cirrhosis and ascites. The objective of the present study is to evaluate the role of albumin in the management of HE. Materiales and methods:: This is a systematic review of randomized controlled trials that evaluated the use of albumin in adult patients with cirrhosis and HE. The search for eligible studies was performed in MEDLINE, EMBASE, and Cochrane CENTRAL databases until June 2020. The outcomes of interest were the complete reversal of HE and mortality. Meta-analysis was performed using the random effects model, through the Mantel-Haenszel method. Results: This systematic review was registered at the PROSPERO platform (CRD42020194181). The search strategy retrieved 1,118 articles. After reviewing titles and abstracts, 24 studies were considered potentially eligible, but 22 were excluded after full-text analysis. Finally, 2 studies were included. In the meta-analysis, albumin was associated to significant lower risks of persistent HE (risk ratio - RR = 0.60; 95% confidence interval - CI = 0.38-0.95, p = 0.03) and mortality (RR = 0.54; 95% CI = 0.33-0.90, p = 0.02). Conclusion: Albumin administration improves HE and reduces mortality in patients with cirrhosis and HE.
Topics: Administration, Oral; Albumins; Hepatic Encephalopathy; Humans; Quality of Life
PubMed: 34600143
DOI: 10.1016/j.aohep.2021.100541 -
Chemical & Pharmaceutical Bulletin 2022Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high... (Review)
Review
Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high biocompatibility, and a wide variety of drug binding abilities. Albumin is known to distribute widely in the blood and various interstitial fluids and organs. Different albumin receptors skillfully regulate the distribution characteristics of albumin in the body. Albumin receptors are a group of diverse proteins, such as FcRn, gp60, gp18, megalin, cubilin, SPARC, and CD36. Their tissue distributions in vivo are unique, with different albumin's recognition sites. Therefore, the distribution of albumin in vivo is ingeniously controlled by these multiple albumin receptors. Reevaluation of these albumin receptors opens up new possibilities for applying albumin as a drug delivery carrier. If the tissue distributions of albumin receptors were known and the albumin recognition site of the receptor was identified, organ-specific active targeting would be possible. In this review, we would like to scrutinize what is currently known and share information to develop next-generation albumin carriers that focus on interactions with albumin receptors.
Topics: Albumins; Drug Delivery Systems; Excipients; Humans; Receptors, Albumin; Tissue Distribution
PubMed: 35491188
DOI: 10.1248/cpb.c21-01024 -
World Journal of Surgical Oncology Jan 2020Provide an updated and comprehensive evaluation of the prognostic value of the albumin-fibrinogen ratio (AFR) and the fibrinogen-prealbumin ratio (FPR) for patients with... (Review)
Review
OBJECTIVE
Provide an updated and comprehensive evaluation of the prognostic value of the albumin-fibrinogen ratio (AFR) and the fibrinogen-prealbumin ratio (FPR) for patients with cancer.
MATERIALS AND METHODS
Four databases (PubMed, Web of Science, Cochrane Library, and WanFang) were searched. The primary endpoints were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Pooled data were synthesized using StataMP 14 and expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS
This update examined 19 studies (7282 cases) that assessed the correlation of AFR with cancer prognosis. Pooled univariate and multivariate analyses indicated significant correlations of low AFR with poor OS (HR 2.18, 95%CI 1.87-2.55 and HR 1.75, 95%CI 1.54-2.00, respectively), poor DFS (HR 1.89, 95%CI 1.54-2.32 and HR 1.51, 95%CI 1.29-1.76, respectively), and poor PFS (HR 1.68, 95%CI 1.42-1.99 and HR 1.48, 95%CI 1.16-1.88, respectively). Pooled univariate and multivariate analyses of 6 studies (2232 cases) indicated high FPR significantly correlated with poor OS (HR 2.37, 95%CI 2.03-2.77 and HR 1.97, 95%CI 1.41-2.77, respectively). One study reported that high FPR correlated with poor DFS (univariate analysis: HR 2.20, 95%CI 1.35-3.57; multivariate analysis: HR 1.77, 95%CI 1.04-2.99) and one study reported a correlation of high FPR with poor PFS in univariate analysis alone (HR 1.79, 95%CI 1.11-2.88).
CONCLUSION
A low AFR and a high FPR correlated with increased risk of cancer mortality and recurrence. AFR and FPR may be promising prognostic markers for cancers.
Topics: Albumins; Biomarkers, Tumor; Fibrinogen; Humans; Neoplasms; Prealbumin; Prognosis
PubMed: 31931816
DOI: 10.1186/s12957-020-1786-2 -
Molecules (Basel, Switzerland) Dec 2022Mulberry powder was created from the extract using a foam-mat drying process. The studies aimed to evaluate the effects of egg albumin, carboxymethyl cellulose (CMC),...
Mulberry powder was created from the extract using a foam-mat drying process. The studies aimed to evaluate the effects of egg albumin, carboxymethyl cellulose (CMC), digestion-resistant maltodextrin (DRM) contents, and whipping time (5 to 15 min) on the foam properties. The impact of different drying temperatures (60 to 75 °C) on the quality of the finished mulberry powder was also noted. The best foam expansion/stability value was determined using multiple regression models as a function of egg albumin, CMC, DRM, and whipping time. The results indicated that the main influencing factors for the foam properties were whipping time followed by egg albumin, CMC, and DRM. Optimum values of foam expansion and stability were achieved at 467.9% and 97.02%, respectively. The foam had a porous structure and good stability for subsequent drying, with optimal contents of egg albumin, CMC, and DRM used at 7.6%, 0.4%, and 2%, respectively, along with a whipping time of 14.5 min. The established models had a high coefficient of determination (R2 > 0.9) and a high correlation between the predicted and observed values. Therefore, the model could be adjusted to determine the characteristics of the foam suitable for subsequent drying. The optimal values were then also verified. Minimal fluctuations (1.78−2.98%) between the experimental data and the optimal value were found. The drying temperature also significantly affected the quality of the mulberry powder. The foam was dried at 65 °C for 4 h to produce apowder with a beautiful light color (L* = 62.65), a characteristic purple-red color of mulberry (a* = 5.97). The moisture, water activity, and anthocyanin content of the finished mulberry powder were 4.57%, 0.3, and 5.4 mg/g, respectively.
Topics: Morus; Desiccation; Fruit; Powders; Plant Extracts; Albumins
PubMed: 36500660
DOI: 10.3390/molecules27238570