Therapeutic Potential of Iron Chelators in Viral Diseases: A Systematic Review.

BACKGROUND: Iron chelators (ICs) have recently emerged as one of the new methods of treatment for viral infections. This study aimed to evaluate the efficiency and safety of natural ICs compared to synthetic ICs. Natural and synthetic ICs are the most common therapeutic agents tested for the treatment of viral infections. When evaluated against synthetic ICs, natural ICs are probably favored owing to their lower toxicity and safer properties. The main objective of the present systematic review was to assess the current evidence on the role of pharmacological mechanisms in the treatment of viral infections. METHOD: This study was designed as a systematic review in which search strategies were focused on two electronic databases, PubMed, and Scopus, between 2017 and 2021. A search filter with two subjects, "iron chelators" and "viral infection", was employed. RESULTS: According to the results, both natural and synthetic chelators had a considerable impact on the treatment of viral infections via various mechanisms, with natural ICs being the most extensively used. CONCLUSION: Natural and synthetic ICs exert their effects through different pharmacological mechanisms. Among these compounds, natural chelators are more widely used due to their safety, efficacy, and a wider range of applications.

Absorption enhancer approach for protein delivery by various routes of administration: a rapid review.

As bioactive molecules, peptides and proteins are essential in living organisms, including animals and humans. Defects in their function lead to various diseases in humans. Therefore, the use of proteins in treating multiple diseases, such as cancers and hepatitis, is increasing. There are different routes to administer proteins, which have limitations due to their large and hydrophilic structure. Another limitation is the presence of biological and lipophilic membranes that do not allow proteins to pass quickly. There are different strategies to increase the absorption of proteins from these biological membranes. One of these strategies is to use compounds as absorption enhancers. Absorption enhancers are compounds such as surfactants, phospholipids and cyclodextrins that increase protein passage through the biological membrane and their absorption by different mechanisms. This review focuses on using other absorption enhancers and their mechanism in protein administration routes.

Fabrication and characterization of lipopeptide biosurfactant-based electrospun nanofibers for use in tissue engineering.

Nanofibers are a class of nanomaterial with specific physicochemical properties and characteristics making them quite sought after and investigated by researchers. Lipopeptide biosurfactant (LPB) formulation properties were previously established in wound healing. LPB were isolated from in vitro culture of Acinetobacter junii B6 and loaded on nanofibers formulation produced by electrospinning method with different ratios of carboxymethylcellulose (CMC), polyvinyl alcohol (PVA), and Poloxamer. Numerous experimental control tests were carried out on formulations, including physicochemical properties which were evaluated by using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), morphology study by scanning electron microscopy (SEM), and thermal stability. The best nanofibers formulation was obtained by the electrospinning method, with a voltage of 19.8 volts, a discharge capacity of 1cm/h, a cylindrical rotating velocity of 100rpm, and a needle interval of 7cm from the cylinder, which continued for 7hours. The formulation contained 2% (w/v) CMC, 10% (w/v) poloxamer, 9% (w/v) PVA, and 5% (w/v) LPB. This formula had desirable physicochemical properties including spreadability, stability, and uniformity with the particle size of about 590nm.

Effectiveness of biosurfactant lipopeptide adhesive mucus paste on the healing process of oral wounds: a randomized controlled trial.

INTRODUCTION: Recurrent aphthous stomatitis is a common lesion of the oral cavity, and many treatments have been introduced by researchers. OBJECTIVE: This study aims to determine the effect of biosurfactant lipopeptide (Acinetobacter baumannii and Pseudomonas aeruginosa) adhesive mucus paste on the healing process of oral wounds. MATERIALS AND METHODS: The studied population included 36 people (age range, 20-41 years). The volunteers had a history of oral ulcers and were randomly assigned to 3 groups: positive control (mouthwash chlorhexidine 0.2%), biosurfactant lipopeptide mucoadhesive (A baumannii and P aeruginosa), and base groups. In this analysis, the 2-paired sample t test, ANOVA, and Kruskal-Wallis test (Wilcoxon signed-rank test) were used. RESULTS: On the second day of treatment, the efficacy index of the positive control group was higher than that of the mucoadhesive and the base groups (P = .04) and there was a significant difference between the mucoadhesive group and the positive control group compared with the base group (P = .001). On the sixth day of treatment, the positive control group was significantly different from the mucoadhesive and base groups in terms of wound size (P < .05). CONCLUSIONS: This study showed that the use of mucoadhesive gel formation containing lipopeptide biosurfactant reduces pain and wound size compared to mucoadhesive without biosurfactant lipopeptide treatment, but it has less effect than routine treatment. Therefore, other studies should be done.

Different applications of temperature responsive nanogels as a new drug delivery system mini review.

Temperature-sensitive drug delivery systems (TSDDS) are one of the systems that have received more attention in medical science these days due to their advantages. As these systems are sensitive to temperature, drug delivery to the target becomes more specific. Temperature-sensitive nanogels have many applications, including microbial infections, cancer therapy, transdermal use, and tissue repair. These systems are characterized by minimal toxicity, improved therapeutic efficacy, and reduced exposure to normal cells. This mini-review is prepared with different types of temperature-sensitive nanogel formation, release mechanisms, and their different applications. Various systems reported under these categories for targeted and controlled delivery of different classes of drugs, such as anti-cancer and antibiotic drugs with special emphasis on anti-cancer drugs and tissue healing, are discussed in this mini-review.

The role of surfactants and biosurfactants in the wound healing process: a review.

Wound healing refers to the complex process of restoring the forms and functions of damaged tissues. Multiple growth factors and released cytokines tightly regulate the wound site. Healing processes can be disrupted by any alteration that would aggravate the damage and lengthen the repair process. Some of the conditions that may impair wound healing include infections and inflammation. Surfactants are amphiphilic compounds widely used in various formulations including detergents, food, pharmaceuticals and cosmetics. Biosurfactants, therefore, are surface-active compounds produced by biological agents, particularly yeast or bacteria, and represent a safer and environmentally preferred alternative to chemical surfactants. Numerous studies have targeted surface-active molecules as wound healing agents for their anti-inflammatory, antioxidant and antibacterial potential. This review focuses on surface-active molecules used in wound healing activities and analyses their effectiveness and mechanisms of action.

Application of plant-derived exosome-like nanoparticles in drug delivery.

Exosomes are one type of extracellular vesicles with size ranging from 30 to 150 nm, which are involved in intercellular communication by transporting specific proteins, nucleic acids, and low molecular weight metabolites. The size and competence of exosomes to transfer biological materials to recipient cells have made them suitable for biomedical use. Therefore, exosomes have been studied as drug delivery systems for various diseases due to low immunogenicity, preferred tumor homing, innate and acquired targetability, and stability. They are secreted by almost all cells from multivesicular endosomes and retrieved in all body fluids including bile, saliva, blood, lymph, urine, cerebrospinal fluid, milk, and etc. Plants' organs also secrete exosomes (Plant-derived exosome-like nanoparticles (PELNs)) which have been considered as an economical and affordable source of production. PELNs are pharmacologically rich in active molecules because of owning unique compositional and morphological features and they can be used as natural nano-carrier for transporting exogenous molecules. In this review, the bio-component and the applications of PELNs as drug delivery systems in neural disorders, tumor-targeted delivery, and gene delivery have been reviewed in different plants such as aloe, turmeric, ginger, lemon, grapefruit, grape, and strawberry.

Cellulose derivatives and natural gums as gelling agents for preparation of emulgel-based dosage forms: A brief review.

Incorporation of an emulsion onto a gel base develops a drug delivery system with improved characteristics, known as emulgel, that can envelop both hydrophilic and lipophilic molecules, and therefore increase stability and penetration of topical formulations. Such a drug delivery system provides controlled drug release that has more patient compliance and higher therapeutic efficacy. Emulgel is prepared in three main stages, preparation of water-in-oil or oil-in-water emulsion, providing the gel base, and incorporation of prepared emulsion onto gel base with continuous stirring. Various materials such as different oils (e.g. sesame oil, balsam oil, and mineral oil), emulsifiers (e.g. Tween® and Span® as the non-ionic surfactant, polyvinyl alcohol), and gelling agents including cellulose derivatives such as hydroxypropyl methylcellulose (HPMC), hydroxyethylcellulose (HEC) and carboxymethyl cellulose (CMC) in different concentrations are used in emulgel preparation. The physical properties, particle size distribution, spreadability, permeation, and drug release rate are evaluated in their development and characterization. They are used in skin disorders and other diseases such as chronic anal fisher. Also, anti-acne, analgesic, and anti-inflammatory drugs have been formulated as emulgel delivery system and their effects have been studied. In this article, the subject is to review the characteristics, preparation methods, and therapeutic efficacy as well as the potential clinical use of emulgels.

Rosemary as an adjunctive treatment in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Rosemary has shown antidepressant and anxiolytic properties. Thus, the present study aimed at assessing the therapeutic effects of orally administered rosemary capsules in patients with major depressive disorder. MATERIALS AND METHODS: Rosmarinic acid content of rosemary was determined using high performance liquid chromatography method. Hard gelatin capsules of rosemary were prepared, and their physicochemical properties were assessed. In this clinical trial, patients with major depressive disorder were randomly divided into rosemary and control groups. They received one capsule of rosemary or placebo twice a day for 8 weeks. The anxiety subscale of Hospital Anxiety and Depression Scale and Beck Depression Inventory - Second Edition were respectively used to measure the symptoms of anxiety and depression in the patients before initiating the treatment and four and eight weeks after the treatment. RESULTS: The amount of rosmarinic acid in rosemary was found to be 21.13 ± 0.56 mg/g dried plant. The scores of anxiety subscale of Hospital Anxiety and Depression Scale and Beck Depression Inventory significantly decreased in the rosemary group compared to those in the control group 8 weeks after the treatment. Memory improvement was a beneficial side effect observed in the study. CONCLUSION: The use of rosemary as an adjunctive therapy could improve the symptoms of anxiety and depression in people with major depression.

pH-Sensitive Polymer-Based Carriers as a Useful Approach for Oral Delivery of Therapeutic Protein: A Review.

There are many proteins and enzymes in the human body, and their dysfunction can lead to the emergence of a disease. The use of proteins as a drug is common in various diseases such as diabetes. Proteins are hydrophilic molecules whose spatial structure is critical to their correct function. There are different ways for the administration of proteins. Protein structures are degraded by gastric acid and enzymes in the gastrointestinal tract and have a slight ability to permeate from the gastrointestinal epithelium due to their large hydrophilic nature. Therefore, their oral use has limitations. Since the oral route for the administration of drugs is one of the best and easiest routes for patients, many studies have been done to increase the stability, penetration, and ultimately, the bioavailability of proteins through oral administration. One of the studied strategies for oral delivery of protein is the use of pH-sensitive polymer-based carriers. These carriers use different pH-sensitive polymers, such as eudragit®, chitosan, dextran, and alginate. The use of pH-sensitive polymer- based carriers by protecting the protein from stomach acid (low pH) and degrading enzymes, increasing permeability and maintaining the spatial structure of the protein, leads to increased bioavailability. In this review, we focus on the various polymers used to prepare pH-sensitive polymer- based carriers for the oral delivery of proteins.

Development of a new electrochemical DNA biosensor based on Eu3+-doped NiO for determination of amsacrine as an anti-cancer drug: Electrochemical, spectroscopic and docking studies.

The present research reported a new electrochemical biosensor based on ds-DNA/Eu3+ doped NiO/CPE to detect amsacrine. Therefore, UV-Vis spectrophotometry, docking, and differential pulse voltammetry (DPV) have been used to study the interactions between amsacrine and dsDNA. Then, experimental parameters affected DNA immobilization and interactions between amsacrine and ds-DNA have been optimized. Afterwards, guanine oxidation peak current of ds-DNA has been chosen as a signal to analyze amsacrine in a concentration ranging between 0.1 and 100.0 µM and finally, limit of detection (LOD) of 0.05 µM has been calculated at optimal condition. Ultimately, it was found that the suggested biosensor is able to determine amsacrine in human serum and urine samples successfully.

Potential Use of Microbial Surfactant in Microemulsion Drug Delivery System: A Systematic Review.

BACKGROUND: Microemulsions drug delivery systems (MDDS) have been known to increase the bioavailability of hydrophobic drugs. The main challenge of the MDDS is the development of an effective and safe system for drug carriage and delivery. Biosurfactants are preferred surface-active molecules because of their lower toxicity and safe characteristics when compared to synthetic surfactants. Glycolipid and lipopeptide are the most common biosurfactants that were tested for MDDS. The main goal of the present systematic review was to estimate the available evidence on the role of biosurfactant in the development of MDDS. SEARCH STRATEGY: Literature searches involved the main scientific databases and were focused on the period from 2005 until 2017. The Search filter composed of two items: "Biosurfactant" and/or "Microemulsion." INCLUSION CRITERIA: Twenty-four studies evaluating the use of biosurfactant in MDDS were eligible for inclusion. Among these 14 were related to the use of glycolipid biosurfactants in the MDDS formulations, while four reported using lipopeptide biosurfactants and six other related review articles. RESULTS: According to the output study parameters, biosurfactants acted as active stabilizers, hydrophilic or hydrophobic linkers and safety carriers in MDDS, and among them glycolipid biosurfactants had the most application in MDDS formulations. CONCLUSION: Synthetic surfactants could be replaced by biosurfactants as an effective bio-source for MDDS due to their excellent self-assembling and emulsifying activity properties.

Antimicrobial, anti-biofilm, and anti-proliferative activities of lipopeptide biosurfactant produced by Acinetobacter junii B6.

Lipopeptide biosurfactants (LPBs) are amphiphilic compounds produced by microorganisms exhibiting various biological activities. The main aim of the present study was to assess the in vitro antimicrobial, anti-biofilm, and cytotoxic effects of LPB produced by Acinetobacter junii (AjL). We determined AjL minimum inhibitory concentration (MIC) against both Gram-positive and Gram-negative bacteria as well as two fungal strains. Also, the anti-biofilm activity of AjL against the biofilm produced by clinically isolated bacterial strains was investigated. The AjL non-selectively showed activity against both Gram-positive and Gram-negative bacterial strains. The obtained results of the present study exhibited that the AjL in concentrations nearly below critical micelle concentration (CMC) has an effective antibacterial activity. It was found that the MIC values of AjL were lower than standard antifungal and it exhibited nearly 100% inhibition against Candida utilis. The attained results of the biofilm formation revealed that AjL disrupted the biofilm of Proteus mirabilis, Staphylococcus aureus, and Pseudomonas aeruginosa at 1250 µg/ml and 2500 µg/ml concentrations. The attained results of cytotoxic effect (determined by WST-1 assay) of the AjL revealed IC50 of 7.8 ±â€¯0.4 mg/ml, 2.4 ±â€¯0.5 mg/ml, and 5.7 ±â€¯0.1 mg/ml, against U87, KB, and HUVEC cell lines, respectively. The results indicated that AjL has a potential application in the relatively new field of biomedicine.

Chitosan-based advanced materials for docetaxel and paclitaxel delivery: Recent advances and future directions in cancer theranostics.

Paclitaxel (PTX) and docetaxel (DTX) are key members of taxanes with high anti-tumor activity against various cancer cells. These chemotherapeutic agents suffer from a number of drawbacks and it seems that low solubility in water is the most important one. Although much effort has been made in improving the bioavailability of PTX and DTX, the low bioavailability and minimal accumulation at tumor sites are still the challenges faced in PTX and DTX therapy. As a consequence, bio-based nanoparticles (NPs) have attracted much attention due to unique properties. Among them, chitosan (CS) is of interest due to its great biocompatibility. CS is a positively charged polysaccharide with the capability of interaction with negatively charged biomolecules. Besides, it can be processed into the sheet, micro/nano-particles, scaffold, and is dissolvable in mildly acidic pH similar to the pH of the tumor microenvironment. Keeping in mind the different applications of CS in the preparation of nanocarriers for delivery of PTX and DTX, in the present review, we demonstrate that how CS functionalized-nanocarriers and CS modification can be beneficial in enhancing the bioavailability of PTX and DTX, targeted delivery at tumor site, image-guided delivery and co-delivery with other anti-tumor drugs or genes.

Hydrogels For Peptide Hormones Delivery: Therapeutic And Tissue Engineering Applications.

Peptides are the most abundant biological compounds in the cells that act as enzymes, hormones, structural element, and antibodies. Mostly, peptides have problems to move across the cells because of their size and poor cellular penetration. Therefore, a carrier that could transfer peptides into cells is ideal and would be effective for disease treatment. Until now, plenty of polymers, e.g., polysaccharides, polypeptides, and lipids were used in drug delivery. Hydrogels made from polysaccharides showed significant development in targeted delivery of peptide hormones because of their natural characteristics such as networks, pore sizes, sustainability, and response to external stimuli. The main aim of the present review was therefore, to gather the important usages of the hydrogels as a carrier in peptide hormone delivery and their application in tissue engineering and regenerative medicine.

Investigation of the structural, physicochemical properties, and aggregation behavior of lipopeptide biosurfactant produced by Acinetobacter junii B6.

In the present study the produced biosurfactant of Acinetobacter junii B6 (recently isolated from Iranian oil excavation site) were partially purified and identified by high performance thin layer chromatography (HPTLC), Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (1H NMR). Elemental analysis of the biosurfactant by energy dispersive X-ray spectroscopy (EDS) revealed that the biosurfactant was anionic in nature. The physiochemical properties of the lipopeptide biosurfactant were evaluated by determination of its critical micelle concentration (CMC) and hydrophile-lipophile balance (HLB). The produced biosurfactant decreased the surface tension of water to 36mNm-1 with the CMC of approximately 300mg/l. Furthermore, the solubility properties of the biosurfactant (dissolved in phosphate-buffer saline solution, pH7.4) were investigated by turbidity examination, dynamic light scattering (DLS) measurements, and transmission electron microscopy (TEM) inspection. It could be concluded that the biosurfactant showed the spherical-shaped vesicles at a concentration higher than its CMC and the circular dichroism (CD) spectra showed that the secondary structure of the biosurfactant vesicles is dominated by the ß sheet.

Antioxidant Potential and Wound Healing Activity of Biosurfactant Produced by Acinetobacter junii B6.

BACKGROUND: Recently, the development of a safe bioactive material with antioxidant properties, which can improve healing activity are focusing. Biosurfactants are very famous for their antimicrobial and free radical scavenging activities. Thereof, the main aim of the present study was to investigate the antioxidant and wound healing activity of the lipopeptide biosurfactant (LBS) produced by Acinetobacter junii B6. DPPH radical scavenging activities and FRAP assays were used to measure the antioxidant properties. METHODS: For evaluation of the wound healing activity, 36 rats (previously wounded in depilated thoracic region) were randomly distributed into six groups and chromatic, wound contraction, and histopathological feature were examined. The assessment levels of reactive oxygen species (ROS) after LBS exposure were determined using malondialdehyde (MDA), hydrogen peroxide (H2O2), and glutathione (GSH) assay kits. RESULTS: DPPH assay showed notable scavenging activities at the corresponding concentrations with IC50 value of 0.7 mg/ml. The reductive potency of the LBS showed lower performance at low concentration, while exhibited a remarkable increase at higher concentration. The best histopathological remission was achieved following treatment by 5 mg/ml of the LBS. Scar wounds at day 13 showed the lowest lesion sizes, increased re-epithelialization, hair follicle detection, and decreased amounts of neutrophilic inflammation, immaturity of the wound bed, erythema, edema, capillary, and retention of necrotic tissue. CONCLUSION: Results from MDA, H2O2, and GSH levels of the treated sample confirmed the scavenging property of the bacterial derived LBS through ROS. It could be concluded that the pharmaceutical formula encourages the wound healing because of its notable antioxidant capacity. HIGHLIGHTS: • DPPH and FRAP assays showed notable scavenging activity. • MDA, H2O2, and GSH; confirmed the scavenging property of the derived biosurfactant through ROS. • Synthesized formula encourages the healing of the wound because of its antioxidant capacity.

Evaluation the thermodynamic behavior of nonionic polyoxyethylene surfactants against temperature changes.

Micellization is the most important property of surface agents. It plays an important role in the manufacture of pharmaceutical products. The surfactants have many applications in industry, agriculture, mining and oil recovery with functional properties as wetting, foaming and emulsifier in pharmaceutical and cosmetic products. The micellization parameters of surfactants help the manufacture of pharmaceutical products to be appropriate and stable. Therefore, in this study, Polyoxyethylene lauryl ether (C12E23), Polyoxyethylene (10) cetyl ether (C16E10) and Polyoxyethylene (20) cetyl ether (C16E20) were chosen as the nonionic surfactants to examine the effect of temperature variation (10-80(°)C) on the Critical Micelle Concentration (CMC). The measurement of surface tension was done by a Du Nöuys ring method. The value of CMC was obtained from the surface tension vs. surfactant concentration curve. Since the temperature was increased, the CMC initially decreased and then increased for each surfactant because the formation of the hydrogen bond is harder in the high temperatures. The surface tension γCMC for all three surfactant solutions decreased monotonically as the temperature increased. δG(°)m, ΔH(°)m and ΔS°m as the thermodynamic parameters of micellization, were also estimated and analyzed. The ΔG(°)m was decreased (10-80(°)C) if the temperature was increased. The entropy and enthalpy correlation of micellization showed a significant linearity. For C12E23, C16E20 and C16 E10, the compensation temperature (Tc) was obtained 309.5, 313.2 and 314.4 K, respectively. The calculated thermodynamic parameters showed that the entropy influenced on the micellization process at lower temperature, but it affected by enthalpy when temperature was increased.