Effect of l -Dopa in acute temozolomide-induced cognitive impairment in male mice: a possible antineuroinflammatory role.

Temozolomide is used commonly in the treatment of some types of cancers, but it may also result in cognitive impairments such as memory deficits. l -Dopa, a well known medicine for the central nervous system, has been shown to have positive effects on some cognitive disorders. Here we sought to investigate the effect of l -Dopa on temozolomide-induced cognitive impairments. BALB/c mice were subjected to 3-days temozolomide and 6-days concomitant l -Dopa/benserazide administration in six groups (control, l -Dopa 25 mg/kg, l -Dopa 75 mg/kg, temozolomide, temozolomide +  l -Dopa 25 mg/kg, and temozolomide +  l -Dopa 75 mg/kg). Open field test, object location recognition, novel object recognition test, and shuttle-box test were carried out to determine the locomotor, anxiety-like behavior, and memory function of subjects. TNF-α and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was measured by real-time PCR. Mice treated with temozolomide showed recognition memory impairment, along with hippocampal TNF-α and BDNF mRNA expression level raise, and detection of histological insults in hematoxylin and eosin hippocampal slides. Mice that received temozolomide +  l -Dopa showed normal behavioral function and lower TNF-α and BDNF hippocampal mRNA expression levels, and histologically normal hippocampal CA1 region in comparison with mice in the temozolomide group. Our results provide evidence that l -Dopa prevents temozolomide-induced recognition memory deficit in mice at the acute phase probably via l -Dopa antineuroinflammatory effects.

Assessment of the Effect of Sub-Cutaneous Adalimumab on Prognosis of COVID-19 Patients: a Non-Randomized Pilot Clinical Trial Study in Iran.

BACKGROUND: Adalimumab is an anti-inflammatory medicine used to treat a variety of disorders, although its effectiveness in improving the clinical status of COVID-19 patients is debatable. The goal was to evaluate the efficacy of adalimumab as an alternate treatment in COVID-19 patients. METHODS: This non-randomized pilot clinical trial study included 18 patients with severe COVID-19 status hospitalized at the Afzalipour Hospital in Kerman from February 2022 to March 2022. Patients were divided into two groups: nine patients in the control group received dexamethasone, remdesivir, and heparin in addition to supportive therapies. The case group also included nine patients who received adalimumab injection (CinnoRA®, CinnaGen, Iran) in addition to the treatment administered to the control group. RESULTS: Although the effect of adalimumab injection on clinical factors, including mechanical ventilation required, the number of days oxygen needed, the length of stay in the intensive care unit (ICU), and saturation of peripheral oxygen (SpO2) level and respiratory rate (RR), were not significantly different between groups, the intra-group SpO2 level before and after receiving oxygen was significantly different in the case group (p ≤ 0.001 and p = 0.002). In addition, laboratory tests for lactate dehydrogenase (LDH) and C-reactive protein (CRP) revealed no statistically significant differences between the two groups. Nonetheless, a positive intra-group effect of the medication was detected on these two parameters. No short-term side effects of drug injection were observed. CONCLUSIONS: This study demonstrated the efficacy of adalimumab as an alternate medication for improving SpO2, LDH, and CRP levels in COVID-19 patients.

3D-QSAR, molecular docking, molecular dynamics, and ADME/T analysis of marketed and newly designed flavonoids as inhibitors of Bcl-2 family proteins for targeting U-87 glioblastoma.

Glioblastoma is the most common and destructive brain tumor with increasing complexity. Flavonoids are versatile natural compounds with the approved anticancer activity, which could be considered as a potential treatment for glioblastoma. A quantitative structure-activity relationship (QSAR) can provide adequate data for understanding the role of flavonoids structure against glioblastoma. The IC50 of various flavonoids for the U-87 cell line was used to prepare an adequate three-dimensional QSAR (3D-QSAR) model. The validation of the model was carried out using some statistical parameters such as R2 and Q2 . Based on the QSAR model, the activities of other marketed and newly designed flavonoids were predicted. Molecular docking study and molecular dynamics (MD) simulation were conducted for better recognition of the interactions between the most active compounds and Bcl-2 family proteins. Moreover, an AMDE/T analysis was performed for the most active flavonoids. A reliable 3D-QSAR was performed with R2 and Q2 of 0.91 and 0.82. The molecular docking study revealed that BCL-XL has a higher binding affinity with the most active compounds, and the MD simulation showed that some residues of the BH3 domain, such as Phe97, Tyr101, Arg102, and Phe105 create remarkable hydrophobic interactions with the ligands. ADME/T analysis also showed the potential of the active compounds for further investigation. 3D-QSAR study is a beneficial method to evaluate and design anticancer compounds. Considering the results of the molecular docking study, MD simulation, and ADME/T analysis, the designed compound 54 could be considered as a potential treatment for glioblastoma.

The Prevalence of Polypharmacy and Potential Drug-Drug Interactions among Iranian Cancer Patients: Which Patients were at Risk?

INTRODUCTION: Drug-Drug interactions (DDIs) are one of the considerable consequences of polypharmacy. Due to the influence of polypharmacy and drug interactions on cancer treatment and patients` health outcomes, this study aimed to determine the prevalence of polypharmacy and potential DDIs among adult cancer patients in Kerman province, southeast of Iran. METHODS: In this cross-sectional study, 315 cancer patients who referred to Kerman city oncology clinics were assessed in 2018. Data were collected through face-to-face interviews and medical charts were reviewed. Polypharmacy was defined as the use of at least five drugs simultaneously. Potential DDIs were checked using the "Drugs.com" online database. A bivariable and a multivariable logistic regression were used to determine the associated factors of outcome variables, polypharmacy status, and potential DDI in SPSS software version 23. RESULTS: Of 315 cancer patients, 191 patients (60.6%; 95% CI: 54.9, 66) used at least five drugs during chemotherapy courses. The prevalence of potential DDIs was 59.6% (n = 140, 95% confidence interval [CI]: 53.6-66.0. Experience co-morbid diseases (OR: 6.60; 95% CI: 3.82, 11.42; p value ≤ .0001), and positive metastatic status (OR: 2.80; 95% CI: 1.62, 4.82; p value ≤ .0001) could predict the polypharmacy during chemotherapy courses. Patients who suffered gastrointestinal cancers (OR: 5.55; 95% CI: 2.26, 13.62; p value ≤ .0001) and the number of prescribed or Over The Counter (OTC) drugs (OR: 1.29; 95% CI: 1.12, 1.48; p value < .0001) predicted the occurrence of potential DDIs among cancer patients. CONCLUSIONS: Regarding the high prevalence of polypharmacy and potential drug interactions among Iranian cancer patients during chemotherapy courses, it is advisable for physicians, nurses, and pharmacists to be vigilant to improve prescribing patterns. In addition, with intensive monitoring, alternative treatment strategies can be replaced.

[TBP]2SO4 ionic liquid catalyst for 4MCR of pyridazinoindazole, indazolophthalazine and pyrazolophthalazine derivatives.

Tetrabutyl phosphonium sulfate ([TBP]2SO4), as novel room-temperature ionic liquid (RTIL), was synthesized by a simple cost-effective method, characterized by 1H, 13C, 31P NMR and FT-IR spectrophotometry. The newly prepared catalyst was used as an efficient catalyst in some four multicomponent reactions (4MCRs) e. g., to synthesis pyridazino[1,2-a]indazole, indazolo[2,1-b]phthalazine and pyrazolo[1,2-b]phthalazine. This green method has several advantages such as short reaction time, using simple methods to prepare catalysts and products, easy operation and high efficiency of products. In addition, the catalyst can be easily recovered and reused several times with reduced average activity.

The Impact of D614G Mutation of SARS-COV-2 on the Efficacy of Anti-viral Drugs: A Comparative Molecular Docking and Molecular Dynamics Study.

D614G is one of the most reported mutations in the spike protein of SARS-COV-2 that has altered some crucial characteristics of coronaviruses, such as rate of infection and binding affinities. The binding affinity of different antiviral drugs was evaluated using rigid molecular docking. The reliability of the docking results was evaluated with the induced-fit docking method, and a better understanding of the drug-protein interactions was performed using molecular dynamics simulation. The results show that the D614G variant could change the binding affinity of antiviral drugs and spike protein remarkably. Although Cytarabine showed an appropriate interaction with the wild spike protein, Ribavirin and PMEG diphosphate exhibited a significant binding affinity to the mutated spike protein. The parameters of the ADME/T analysis showed that these drugs are suitable for further in-vitro and in-vivo investigation. D614G alteration affected the binding affinity of the RBD and its receptor on the cell surface.

Niosomal virosome derived by vesicular stomatitis virus glycoprotein as a new gene carrier.

Virosomes as membranous vesicles with viral fusion protein in their membrane are versatile vehicles for cargo delivery. The vesicular stomatitis virus glycoprotein (VSV-G) is a common fusogenic protein used in virosome preparation. This glycoprotein has been used in liposomal systems so far, but in this study, we have tried to use the niosomal form instead of liposome for. Niosomes are vesicular systems composed of non-ionic surfactants. Niosomes were constructed by the thin-film hydration method. VSV-G gene in pMD2.G plasmid was expressed in the HEK293T cell line and then was reconstituted in the niosome bilayer. The formation of niosomal virosomes was confirmed with different methods such as SDS-PAGE gel, western blotting, and transmission electron microscopy (TEM). The efficiency of niosomal virosome was investigated with the pmCherry reporter gene. SDS-PAGE and western blotting proved the expression and successful insertion of protein into the bilayer. The TEM images showed the spike projection of VSV-G on the surface of niosomes. The transfection results showed high efficiency of niosomal virosomes as a novel carrier. This report has verified that niosome could be used as an efficient bilayer instead of liposome to construct virosomes.

EMT signaling: potential contribution of CRISPR/Cas gene editing.

Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system has greatly contributed to identify or validate critical genes in pathway signaling. This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance our understanding of the EMT process.

Eco-friendly synthesis of the Li/Al in nonionic surfactant-based vesicles (niosomes) modified with graphene oxide quantum dot nanostructures for controlled released of chlorpheniramine maleate.

The aim of the present work was the preparation of Li/Al nanoparticles (NPs) functionalized with graphene oxide quantum dots (GOQDs) for the controlled release of chlorpheniramine maleate (CPAM). The role of lemon and egg white extracts as oxidation agents were investigated for the morphology and particle size of the products. GOQDs were synthesized using green, environmentally friendly, and cost-effective precursors. This work demonstrates that Li/Al NPs functionalized with graphene oxide as a nanolayer structure can be used as efficient nanocarriers for loading and delivery of CPAM as water-insoluble aromatic drugs The final products were identified with X-ray diffraction, scanning electron microscopy, atomic force microscopy, ultraviolet-visible spectroscopy, dynamic light scattering, thermogravimetric analysis, and transmission electron microscopy nitrogen adsorption [i.e. Brunauer-Emmett-Teller (BET) surface area analysis] techniques. The calibration curve for Li/Al nanoparticles functionalized with GOQDs for controlled released of CPAM was calculated as y = 0.0137x + 0.0103 with R2  = 0.9995. The data found through BET and Barrett-Joyner-Halenda analysis using the adsorption/desorption isotherm method demonstrated by total pore volumes and dead volume were calculated respectively as 0.162 nm2 , 0.0439 cm3 g-1 . The mean pore diameter was calculated as 20.33 nm using BET isotherm data.

Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems.

Topoisomerase enzymes have shown unique roles in replication and transcription. These enzymes which were initially found in Escherichia coli have attracted considerable attention as target molecules for cancer therapy. Nowadays, there are several topoisomerase inhibitors in the market to treat or at least control the progression of cancer. However, significant toxicity, low solubility and poor pharmacokinetic properties have limited their wide application and these characteristics need to be improved. Nano-delivery systems have provided an opportunity to modify the intrinsic properties of molecules and also to transfer the toxic agent to the target tissues. These delivery systems leads to the re-introduction of existing molecules present in the market as novel therapeutic agents with different physicochemical and pharmacokinetic properties. This review focusses on a variety of nano-delivery vehicles used for the improvement of pharmacological properties of topoisomerase inhibitors and thus enabling their potential application as novel drugs in the market.

Nanotechnological Strategies for Osteoarthritis Diagnosis, Monitoring, Clinical Management, and Regenerative Medicine: Recent Advances and Future Opportunities.

PURPOSE OF REVIEW: In this review article, we discuss the potential for employing nanotechnological strategies for the diagnosis, monitoring, and clinical management of osteoarthritis (OA) and explore how nanotechnology is being integrated rapidly into regenerative medicine for OA and related osteoarticular disorders. RECENT FINDINGS: We review recent advances in this rapidly emerging field and discuss future opportunities for innovations in enhanced diagnosis, prognosis, and treatment of OA and other osteoarticular disorders, the smart delivery of drugs and biological agents, and the development of biomimetic regenerative platforms to support cell and gene therapies for arresting OA and promoting cartilage and bone repair. Nanotubes, magnetic nanoparticles, and other nanotechnology-based drug and gene delivery systems may be used for targeting molecular pathways and pathogenic mechanisms involved in OA development. Nanocomposites are also being explored as potential tools for promoting cartilage repair. Nanotechnology platforms may be combined with cell, gene, and biological therapies for the development of a new generation of future OA therapeutics. Graphical Abstract.

Novel CaO/polylactic acid nanoscaffold as dental resin nanocomposites and the investigation of physicochemical properties.

In this study, for the first time, calcium oxide (CaO)/polylactic acid nanoscaffolds were synthesized by co-precipitation assistant reverse micelles method. The physical and chemical (physicochemical) properties of the structures as dental resin composites were also studied. Nanocomposite materials as primary and basic dental compounds can be conveniently applied as dental filling materials with a high esthetic quality. In this research nanoscaffolds act as a bed for nanoparticles and improve the mechanical and chemical (mechanochemical) properties, CaO nanoparticles were loading in polylactic acid nanoscaffold as a bioactivity polymer for usage in the dental resin composites. Mechanical properties of the dental resin composite containing CaO/polylactic acid nanoscaffold were calculated: the flexural strength (137.2 MPa), modulus (12.9GPa) and compressive strength (344.2 MPa). Potential of the basic nanoparticle and the products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-visible) and atomic force microscopy (AFM) showed the size of the optimized nanostructures was about 85 to 120 nm. According to TGA results of polylactic acid nanofibers with thermal stability below 300°C these high thermal stability materials can be used as dental resin composites.

Antileishmanial Activity of Niosomal Combination Forms of Tioxolone along with Benzoxonium Chloride against Leishmania tropica.

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 µg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.

Assessing effectiveness of adding niosomal atorvastatin 1% ointment to topical calcineurin inhibitor treatment in non-segmental vitiligo.

BACKGROUND: Treatment of vitiligo is still a big challenge for dermatologists. The efficacy of statins in the treatment of vitiligo is controversial. AIM AND OBJECTIVE: We studied possible therapeutic effect of topical 1% niosomal atorvastatin ointment combined with topical 0.1% tacrolimus in treatment of non-segmental vitiligo. METHODS: This is a triple blind, pilot, randomized placebo-controlled trial (RCT) that was performed in dermatology clinic. All the patients used topical 0.1% tacrolimus cream twice daily (BD). Moreover, the intervention group participants used topical 1% niosomal atorvastatin ointment, and control group participants were prescribed placebo ointment, BD. Patients were evaluated using vitiligo area surface index (VASI) score and patients' satisfaction at baseline and after 3 months treatment. RESULTS: The mean patient satisfaction in the intervention and control groups were 5 ± 1.4 and 3.5 ± 1.9; the difference between groups was not statistically significant (p = 0.9). We found statistically significant difference in VASI score before and after treatment in both intervention and control groups (p = 0.01 and p = 0.03, respectively). However, comparison of the VASI score between groups was not statistically significant (p = 0.62). We also found no significant correlation between VASI score and other variables. CONCLUSION: The result of this study indicates that adding of niosomal atorvastatin 1% ointment to topical calcineurin inhibitor has no additional effect on non-segmental type of vitiligo. Further large studies with different combinations are recommended before any conclusive result can be concluded on efficacy of statins in vitiligo.

Niosomal Doxycycline and Triamcinolone: A Novel Approach to Minimize Cytotoxicity in Endodontic Medicaments.

Introduction: Mechanical root canal preparations and irrigation solutions are essential for reducing microbial counts in the root canal system. However, these methods do not completely eliminate microorganisms. Intracanal medicaments are used to further decrease microbial counts. This study aims to assess the cytotoxicity of various intracanal medicaments. Materials and methods: In this in vitro study, murine fibroblast cell lines (L929) were cultured in a controlled environment. The MTT assay was employed to evaluate the cytotoxicity of different medicament combinations, including calcium hydroxide and triamcinolone (D1), niosomal doxycycline and triamcinolone (D2), calcium hydroxide (D3), and a combination of doxycycline and triamcinolone (D4). Statistical analysis was performed using ANOVA and Dunnett's test. Results: The results indicated that D1 and D2 had lower cytotoxicity, while D4 exhibited the highest cytotoxicity. D1 was found to be non-cytotoxic up to a concentration of 500 µg/mL over a period of 72 hours. D2 and D3 showed similar effects up to concentrations of 250 µg/mL and 100 µg/mL, respectively, for 72 hours. In contrast, D4 exhibited cytotoxicity at concentrations above 75 µg/mL at 72 hours. Conclusion: This study suggests that encapsulating doxycycline in niosomal structures (D2) reduces cytotoxicity in murine fibroblast cell lines (L929) for at least 24 and 48 hours. These findings offer promising implications for the development of endodontic medicaments with improved biocompatibility.

Synthesis and physicochemical characterization of Zn-Al layered double hydroxides (LDHs) as a delivery system for amphotericin B: In vitro and in silico antileishmanial study.

Leishmaniasis as a widespread neglected vector-borne protozoan disease is a major public health concern in endemic areas due to 12 million people affected worldwide and 60,000 deaths annually. Several problems and side effects in using current chemotherapies leads to progression of new drug delivery systems against leishmaniasis. For instance, layered double hydroxides (LDHs) so-called anionic clays due to their proper characteristics, have been considered recently. In the present study, LDH nanocarriers were prepared using co-precipitation method. Then, the intercalation reactions with amphotericin B were conducted via indirect ion exchange assay. Finally, after characterization of prepared LDHs, the anti-leishmanial effects of Amp-Zn/Al-LDH nanocomposites against Leishmania major were evaluated using an in vitro and in silico model. According to results, current study demonstrated that Zn/Al-NO3 LDH nanocarriers can be used as a new promising delivery system by intercalating amphotericin B into its interlayer space for leishmaniasis treatment by eliminating the L. major parasites by remarkable immunomodulatory, antioxidant and apoptotic effects.

Comparative Efficacy of Analgesics for Pain Relief in Patients with Symptomatic Irreversible Pulpitis Prior to Emergency Endodontic Treatment: A Randomized Controlled Trial.

Introduction: This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis prior to emergency endodontic treatment. Materials and Methods: This clinical trial was conducted on 120 patients with moderate to severe pain due to symptomatic irreversible pulpitis seeking emergency endodontic treatment. The patients were randomly divided into 4 groups to receive Novafen, MA, Celecoxib, and ibuprofen. The pain score of patients was measured before and 1 hour after analgesic intake using a visual analog scale (VAS). The success of analgesic treatment was analyzed by the binary logistic regression model. Results: A total of 117 patients including 76 females and 41 males with a mean age of 30.29 years completed the study and were statistically analyzed. Ibuprofen had the highest analgesic efficacy followed by Novafen, and caused a significantly greater reduction in pain score compared with MA and celecoxib [OR (Ibuprofen vs MA)=1.28, OR (Ibuprofen vs Celecoxib)=3.74, OR (Novafen vs MA)=2.94, OR (Novafen vs Celecoxib)=2.94, P<0.05]. Ibuprofen and Novafen had no significant difference in analgesic efficacy (P>0.05). Baseline pain score was a predictive factor for the success of analgesics (P<0.05). The success of analgesic treatment decreased by 0.68 times with each unit increase in pain score (P<0.05). Gender and age of patients had no significant effect on success of analgesics (P>0.05). Conclusion: Both ibuprofen and Novafen can serve as the analgesics of choice for pain relief in patients with symptomatic irreversible pulpitis with moderate to severe pain when emergency endodontic treatment cannot be immediately performed.

The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses.

BACKGROUND: The concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients. METHODS: This cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16. RESULTS: Of 262 patients (83.2% of the patients) who used herbal medicines, 209 patients [79.8% (95% Confidence Intervals (CI): 75.2 - 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n = 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n = 34, 16.3%) and peppermint (n = 78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43-2.58; P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR = 2.22, 95%CI:1.00-4.94; P-value = 0.04) were some of the predictors of herb-drug interactions among cancer patients. CONCLUSION: Herbal medicine use during chemotherapy was found prevalent among cancer patients; of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

Preparation and evaluation of niosomes containing autoclaved Leishmania major: a preliminary study.

In this study, different positively charged niosomal formulations containing sorbitan esters, cholesterol and cetyl trimethyl ammonium bromide were prepared by film hydration method for the entrapment of autoclaved Leishmania major (ALM). Size distribution pattern and stability of niosomes were investigated by laser light scattering method and ALM encapsulation per cent was measured by the bicinchoninic acid method. Finally, the selected formulation was used for the induction of the immune response against cutaneous leishmaniasis in BALB/c mice. Size distribution curves of all the formulations followed a log-normal pattern and the mean volume diameter was in the range 7.57-15.80 µm. The mean volume diameters were significantly increased by adding Tween to Span formulations (p < 0.05). The percentage of ALM entrapped in all formulations varied between 14.88% and 36.65%. In contrast to ALM, in vivo studies showed that the niosomes containing ALM have a moderate effect in the prevention of cutaneous leishmaniasis in BALB/c mice.

Recent advances in Bio-conjugated nanocarriers for crossing the Blood-Brain Barrier in (pre-)clinical studies with an emphasis on vesicles.

The brain is one of the most challenging organs for drug delivery. It is preserved by the blood-brain barrier (BBB), which controls the transport of components into and out of the brain. Although various approaches have been utilized to cross the BBB, the drug delivery into the brain is still less successful than the other human body parts. Comprehensive knowledge about the mechanisms and functionalities of brain delivery for different components is required to overcome this complex barrier. In this review, we have discussed the BBB structure, its characteristics, and the BBB's mechanisms for transporting components between the brain and blood. Furthermore, the barriers in front of drug delivery systems, the strategies which should be employed for overcoming these barriers, and different pathways for brain targeting are discussed. Then, the drug delivery systems utilized for crossing the BBB, especially nanocarriers and novel approaches, are considered. Finally, the bioconjugated vesicles as versatile nanocarriers that combine the bioconjugation approach and vesicles are reviewed. This review focuses on the biomolecules used in nano vesicular systems for overcoming the BBB. Various biomolecules such as amino acids, peptides, proteins, antibodies, and carbohydrates could be used for bioconjugation. Bioconjugated vesicles like liposomes and niosomes utilize the related receptor or transporter to cross the BBB. These drug delivery systems have shown enhanced drug loading into the brain, which is discussed.