scholarly journals Alginate oligosaccharides can maintain activities of lysosomes under low pH condition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ra-Mi Park ◽  
Ngoc-Han Thi Nguyen ◽  
Su-Min Lee ◽  
Yang-Hoon Kim ◽  
Jiho Min
Keyword(s):  
Oral Administration ◽  
Polyacrylamide Gel Electrophoresis ◽  
Therapeutic Agents ◽  
Low Ph ◽  
Oral Dosage ◽  
Alginate Oligosaccharides ◽  
Composite Form ◽  
Acidic Conditions ◽  
Direct Delivery ◽  
Alginate Oligosaccharide

AbstractThe objective of this study was to report that lysosome extracted from egg white could be used as a drug through oral administration for treating diseases by using pH sensitive alginate oligosaccharides. Lysosome-alginate oligosaccharides composite were formulated for oral administration of lysosomes. The dissolution test confirmed the availability of the oral dosage form. When lysosome were used as an independent drug, the activity of protein was lost due to influence of low pH. Its antibacterial activity was also remarkably reduced. However, when lysosome-alginate oligosaccharides composite form was used, antimicrobial activity of lysozyme was maintained. At low pH, a gel-like matrix was formed by alginate oligosaccharides to protect the lysosome. When the pH was increased, alginate oligosaccharides were dissolved and the lysosome was released. SDS–polyacrylamide gel electrophoresis analysis of released lysosomes revealed that alginate oligosaccharide could effectively protect the lysosome from degradation or hydrolysis under acidic conditions for at least 2 h. The results of this study are important for application of lysosomes as therapeutic agents, and also it was confirmed that alginate oligosaccharides have potential as direct delivery system for the oral application of protein derived therapies.

scholarly journals Advances in Research on the Bioactivity of Alginate Oligosaccharides

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 144 ◽  
Author(s):  
Maochen Xing ◽  
Qi Cao ◽  
Yu Wang ◽  
Han Xiao ◽  
Jiarui Zhao ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Biological Activity ◽  
Theoretical Basis ◽  
Low Molecular Weight ◽  
Brown Seaweeds ◽  
Promote Cell Proliferation ◽  
Natural Polysaccharide ◽  
Alginate Oligosaccharides ◽  
Alginate Oligosaccharide ◽  
Alginate Degradation

Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products.

Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant

2011 ◽  
Vol 105 (06) ◽  
pp. 1060-1071 ◽  
Author(s):  
Jin Woo Park ◽  
Ok Cheol Jeon ◽  
Sang Kyoon Kim ◽  
Taslim Al-Hilal ◽  
Kyung-Min Lim ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Deoxycholic Acid ◽  
Oral Absorption ◽  
Metabolic Stability ◽  
Oral Dosage ◽  
Low Molecular Weight ◽  
Therapeutic Effects ◽  
Oral Tablet

SummaryThis study was designed to develop a solid oral dosage form of deoxycholic acid (DOCA)-conjugated low-molecular-weight heparin (LMWH) and to evaluate its oral absorption, distribution, and metabolic stability for the prospect of providing an orally bioavailable LMWH. The LMWH derivative (LHD) was synthesised and then formulated with solubilisers and other pharmaceutical excipients to form a solid tablet. Its absorption and distribution after oral administration were evaluated in mice, rats, and monkeys. The in vitro metabolic stability of LHD was examined by liver microsome assays. More than 80% of LHD was released from the tablet within 60 minutes, guaranteeing rapid tablet disintegration after oral administration. Oral bioavailability of LHD in mice, rats and monkeys were 16.1 ± 3.0, 15.6 ± 6.1, and 15.8 ± 2.5%, respectively. After the oral administration of 131I-tyramine-LHD, most of the absorbed drug remained in the blood circulation and was eliminated mainly through the kidneys. LHD was hardly metabolised by the liver microsomes and showed a stable metabolic pattern similar to that of LMWH. In a rat thrombosis model, 10 mg/kg of orally administered LHD reduced thrombus formation by 60.8%, which was comparable to the antithrombotic effect of the subcutaneously injected LMWH (100 IU/ kg). Solid tablets of LHD exhibited high oral absorption and statistically significant therapeutic effects in preventing venous thromboembolism. Accordingly, LHD tablets are expected to satisfy the unmet medical need for an oral heparin-based anticoagulant as an alternative to injectable heparin and oral warfarin.

scholarly journals AguR Is Required for Induction of the Streptococcus mutans Agmatine Deiminase System by Low pH and Agmatine

2009 ◽  
Vol 75 (9) ◽  
pp. 2629-2637 ◽  
Author(s):  
Yaling Liu ◽  
Lin Zeng ◽  
Robert A. Burne
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Streptococcus Mutans ◽  
Low Ph ◽  
Binding Domain ◽  
Negative Regulator ◽  
Dna Binding Domain ◽  
Mutant Proteins ◽  
Acidic Conditions ◽  
Agmatine Deiminase

ABSTRACT Acidic conditions and the presence of exogenous agmatine are required to achieve maximal expression of the agmatine deiminase system (AgDS) of Streptococcus mutans. Here we demonstrate that the transcriptional activator of the AgDS, AguR, is required for the responses to agmatine and to low pH. Linker scanning mutagenesis was used to create a panel of mutated aguR genes that were utilized to complement an aguR deletion mutant of S. mutans. The level of production of the mutant proteins was shown to be comparable to that of the wild-type AguR protein. Mutations in the predicted DNA binding domain of AguR eliminated activation of the agu operon. Insertions into the region connecting the DNA binding domain to the predicted extracellular and transmembrane domains were well tolerated. In contrast, a variety of mutants were isolated that had a diminished capacity to respond to low pH but retained the ability to activate AgDS gene expression in response to agmatine, and vice versa. Also, a number of mutants were unable to respond to either agmatine or low pH. AguD, which is a predicted agmatine-putrescine antiporter, was found to be a negative regulator of AgDS gene expression in the absence of exogenous agmatine but was not required for low-pH induction of the AgDS genes. This study reveals that the control of AgDS gene expression by both agmatine and low pH is coordinated through the AguR protein and begins to identify domains of the protein involved in sensing and signaling.

Recent Developments in Medicated Lozenges: A Promising Dosage Form for the Effective Delivery of Therapeutic Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Deepak Sharma ◽  
Dinesh Kumar ◽  
Gurmeet Singh
Keyword(s):  
Retention Time ◽  
Drug Targeting ◽  
Dosage Form ◽  
Base Material ◽  
Rapid Onset ◽  
Oral Route ◽  
Therapeutic Agents ◽  
Oral Dosage ◽  
Onset Of Action ◽  
Pharmaceutical Industries

Background: The delivery of therapeutic agents through the oral route remains the most favorable one as compared to other routes of drug administration. However, numerous disadvantages are encountered in conventional formulations such as low bioavailability, first-pass metabolism, gastric irritation, delayed onset of action, bitter taste, low retention time, frequent dosing, and non-localized drug targeting. All these problems encountered guide the various pharmaceutical industries to manufacture and develop a novel solid oral dosage form called lozenges. Lozenges are solid oral dosage forms of medicament, meant to be dissolved within the mouth or pharynx. It may consist of one or more than one medicinal agent contained in a sweetened and flavored base material. Objective: The present review is focused on various types, compositions, methodologies used to prepare the medicated lozenges and on different evaluation parameters that establish its safety and efficacy. It also put a light on different commercially available and reported medicated lozenges formulation. Method: The various review and research articles reported by different researchers were studied extensively by using the databases of Google Scholar, Pubmed, Scopus, Web of Science and various commercial websites that were also investigated for information regarding new products. Results: Lozenges provides various advantages in terms of patient compliance, rapid onset of action, prolonged retention time, enhancement of bioavailability, ease of manufacturing, localized drug targeting, sustained or controlled effect, and reduced dosing frequency. It has also the ability to incorporate the drugs belong to different therapeutic classes for treating various disorders related to oral cavities like gingivitis, dental plaque, mouth ulcers, throat pain, oral thrush, throat infection, periodontitis, and pharyngitis. However, its applicability is not only limited to localized action, but it has also been employed to deliver the drug systemically for the conditions such as cough, decongestion, runny nose, nausea, vomiting, allergy, low immunity, fever, body ache, the killing of worms and smoking cessation. Conclusion: It was concluded that it has been played an important role in the field of drug delivery and will continue to perform in the same way in the future as well.

scholarly journals Nanopolyphenols: a review of their encapsulation and anti-diabetic effects

2020 ◽  
Vol 2 (8) ◽  
Author(s):  
Theresa F. Rambaran
Keyword(s):  
Functional Food ◽  
Encapsulation Efficiency ◽  
Water Solubility ◽  
Drug Loading ◽  
Therapeutic Agents ◽  
Low Ph ◽  
Free Form ◽  
Pharmaceutical Development ◽  
Curcumin Nanoparticles ◽  
Treatment Of Diabetes

AbstractPolyphenols are believed to possess numerous health benefits and can be grouped as phenolic acids, flavonoids or non-flavonoids. Research involving the synthesis of nanopolyphenols has attracted interest in the areas of functional food, nutraceutical and pharmaceutical development. This is in an effort to overcome current challenges which limit the application of polyphenols such as their rapid elimination, low water-solubility, instability at low pH, and their particle size. In the synthesis of nanopolyphenols, the type of nanocarrier used, the nanoencapsulation technique employed and the type of polymers that constitute the drug delivery system are crucial. For this review, all mentioned factors which can influence the therapeutic efficacy of nanopolyphenols were assessed. Their efficacy as anti-diabetic agents was also evaluated in 33 publications. Among these were phenolic acid (1), flavonoids (13), non-flavonoids (17) and polyphenol-rich extracts (2). The most researched polyphenols were quercetin and curcumin. Nanoparticles were the main nanocarrier and the size of the nanopolyphenols ranged from 15 to 333 nm with encapsulation efficiency and drug loading capacities of 56–97.7% and 4.2–53.2%, respectively. The quantity of nanomaterial administered orally ranged from 1 to 300 mg/kg/day with study durations of 1–70 days. Most studies compared the effect of the nanopolyphenol to its free-form and, in all but three cases, significantly greater effects of the former were reported. Assessment of the polyphenol to understand its properties and the subsequent synthesis of its nanoencapsulated form using suitable nanocarriers, polymers and encapsulation techniques can result in effective therapeutic agents for the treatment of diabetes.

scholarly journals Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 692 ◽  
Author(s):  
Marta Szekalska ◽  
Magdalena Wróblewska ◽  
Monika Trofimiuk ◽  
Anna Basa ◽  
Katarzyna Winnicka
Keyword(s):  
Antifungal Activity ◽  
Sodium Alginate ◽  
Dosage Forms ◽  
Antifungal Drugs ◽  
Oral Dosage ◽  
Future Research ◽  
Swelling Properties ◽  
Promising Alternative ◽  
Alginate Oligosaccharides ◽  
Buccal Films

Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs.

Application of Methanobrevibacter acididurans in anaerobic digestion

2004 ◽  
Vol 50 (6) ◽  
pp. 109-114 ◽  
Author(s):  
D.V. Savant ◽  
D.R. Ranade
Keyword(s):  
Fatty Acids ◽  
Anaerobic Digestion ◽  
Methane Production ◽  
Volatile Fatty Acids ◽  
Low Ph ◽  
Anaerobic Digesters ◽  
Hydrogenotrophic Methanogen ◽  
Distillery Wastewater ◽  
Acid Tolerant ◽  
Acidic Conditions

To operate anaerobic digesters successfully under acidic conditions, hydrogen utilizing methanogens which can grow efficiently at low pH and tolerate high volatile fatty acids (VFA) are desirable. An acid tolerant hydrogenotrophic methanogen viz. Methanobrevibacter acididurans isolated from slurry of an anaerobic digester running on alcohol distillery wastewater has been described earlier by this lab. This organism could grow optimally at pH 6.0. In the experiments reported herein, M. acididurans showed better methanogenesis under acidic conditions with high VFA, particularly acetate, than Methanobacterium bryantii, a common hydrogenotrophic inhabitant of anaerobic digesters. Addition of M. acididurans culture to digesting slurry of acidogenic as well as methanogenic digesters running on distillery wastewater showed increase in methane production and decrease in accumulation of volatile fatty acids. The results proved the feasibility of application of M. acididurans in anaerobic digesters.

scholarly journals Effects of oxygen tension and pH on the respiratory burst of human neutrophils

Blood ◽  
1979 ◽  
Vol 53 (6) ◽  
pp. 1133-1139 ◽  
Author(s):  
TG Gabig ◽  
SI Bearman ◽  
BM Babior
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Concentration ◽  
Respiratory Burst ◽  
Low Ph ◽  
Human Neutrophils ◽  
Respiratory Burst Activity ◽  
Similar Dependence ◽  
Activated Neutrophils ◽  
Acidic Conditions ◽  
O2 Production

Abstract The respiratory burst of human neutrophils was measured under conditions of hypoxia and low pH. O2 -- production by neutrophils activated with opsonized zymosan fell slowly as the oxygen concentration declined to 1%, then dropped more sharply, reaching negligible levels at oxygen concentrations less than 0.25%. Production was half maximal at an oxygen concentration of 0.35% (equivalent to approximately 10-microM dissolved oxygen). O2- production by the cell- free O2- -forming system prepared from zymosan-activated neutrophils showed a similar dependence on oxygen concentration. A drop in pH caused decreases in both oxygen consumption and O2-- production by zymosan-treated neutrophils, values at PH 6.0 being 10%--20% of those observed at pH 7.5. Experiments with the cell-free O2-- -forming system suggested that this decline in respiratory burst activity at low pH was due to inefficient activation of the O2-- -forming enzyme under acidic conditions.

scholarly journals Mono- and Bi-Phasic Cellulose Acetate Micro-Vectors for Anti-Inflammatory Drug Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 87 ◽  
Author(s):  
Vincenzo Guarino ◽  
Rosaria Altobelli ◽  
Tania Caputo ◽  
Luigi Ambrosio ◽  
Sergio Caserta ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Image Analysis ◽  
Oral Administration ◽  
Cellulose Acetate ◽  
Core Shell ◽  
Processing Technologies ◽  
Rheological Study ◽  
Inflammatory Drugs ◽  
Acidic Conditions ◽  
Anti Inflammatory

In recent years, different processing technologies have been engineered to fabricate capsules or particles with peculiar properties (e.g., swelling, pH-sensitive response) at the micro and sub-micrometric size scale, to be used as carriers for controlled drug and molecular release. Herein, the development of cellulose acetate (CA) micro-carriers with mono- (MC) or bi-phasic (BC) composition is proposed, fabricated via electrohydrodynamic atomization (EHDA)—an electro-dropping technology able to micro-size polymer solution by the application of high voltage electrostatic forces. Image analysis allows identification of the process parameters to optimize morphology, in terms of size distribution and shape. Meanwhile, an accurate rheological study has enabled investigating the interface between CA solutions with different viscosities to optimize BC systems. Release tests have confirmed that BC carriers can retain the drug more efficiently in acidic conditions, also providing a more gradual and sustained release until six days, with respect to MC carriers. Hence, all these results have proven that biphasic architecture significantly improves the capability of CA microcarriers to release ketoprofen lysinate, thus suggesting a new route to design core/shell systems for the retarded oral administration of anti-inflammatory drugs.

scholarly journals Purification and properties of adenylyl sulphate:ammonia adenylyltransferase from Chlorella catalysing the formation of adenosine 5′-phosphoramidate from adenosine 5′-phosphosulphate and ammonia

1981 ◽  
Vol 195 (3) ◽  
pp. 545-560 ◽  
Author(s):  
Heinz Fankhauser ◽  
Jerome A. Schiff ◽  
Leonard J. Garber
Keyword(s):  
Molecular Weight ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Deae Cellulose ◽  
Low Ph ◽  
Polyacrylamide Gel ◽  
Ph Optimum ◽  
Unknown Compound ◽  
Reactive Blue 2

Extracts of Chlorella pyrenoidosa, Euglena gracilis var. bacillaris, spinach, barley, Dictyostelium discoideum and Escherichia coli form an unknown compound enzymically from adenosine 5′-phosphosulphate in the presence of ammonia. This unknown compound shares the following properties with adenosine 5′-phosphoramidate: molar proportions of constituent parts (1 adenine:1 ribose:1 phosphate:1 ammonia released at low pH), co-electrophoresis in all buffers tested including borate, formation of AMP at low pH through release of ammonia, mass and i.r. spectra and conversion into 5′-AMP by phosphodiesterase. This unknown compound therefore appears to be identical with adenosine 5′-phosphoramidate. The enzyme that catalyses the formation of adenosine 5′-phosphoramidate from ammonia and adenosine 5′-phosphosulphate was purified 1800-fold (to homogeneity) from Chlorella by using (NH4)2SO4 precipitation and DEAE-cellulose, Sephadex and Reactive Blue 2–agarose chromatography. The purified enzyme shows one band of protein, coincident with activity, at a position corresponding to 60000–65000 molecular weight, on polyacrylamide-gel electrophoresis, and yields three subunits on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of 26000, 21000 and 17000 molecular weight, consistent with a molecular weight of 64000 for the native enzyme. Isoelectrofocusing yields one band of pI4.2. The pH optimum of the enzyme-catalysed reaction is 8.8. ATP, ADP or adenosine 3′-phosphate 5′-phosphosulphate will not replace adenosine 5′-phosphosulphate, and the apparent Km for the last-mentioned compound is 0.82mm. The apparent Km for ammonia (assuming NH3 to be the active species) is about 10mm. A large variety of primary, secondary and tertiary amines or amides will not replace ammonia. One mol.prop. of adenosine 5′-phosphosulphate reacts with 1 mol.prop. of ammonia to yield 1 mol.prop. each of adenosine 5′-phosphoramidate and sulphate; no AMP is found. The highly purified enzyme does not catalyse any of the known reactions of adenosine 5′-phosphosulphate, including those catalysed by ATP sulphurylase, adenosine 5′-phosphosulphate kinase, adenosine 5′-phosphosulphate sulphotransferase or ADP sulphurylase. Adenosine 5′-phosphoramidate is found in old samples of the ammonium salt of adenosine 5′-phosphosulphate and can be formed non-enzymically if adenosine 5′-phosphosulphate and ammonia are boiled. In the non-enzymic reaction both adenosine 5′-phosphoramidate and AMP are formed. Thus the enzyme forms adenosine 5′-phosphoramidate by selectively speeding up an already favoured reaction.

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