1,184 research outputs found
sj-pdf-1-imr-10.1177_03000605221105356 - Supplemental material for Medical laboratory staff satisfaction and their perspective on the role of health institutions to combat COVID-19 pandemic
No full textSupplemental material, sj-pdf-1-imr-10.1177_03000605221105356 for Medical laboratory staff satisfaction and their perspective on the role of health institutions to combat COVID-19 pandemic by Buddha Bahadur Basnet, Deepa Satyal, Roshan Pandit, Anjila Maharjan, Rashmi Karki, Shyam Kumar Mishra, Srijana GC, Til Bahadur Basnet in Journal of International Medical Research</p
Liposomes-in-chitosan hydrogel boosts potential of chlorhexidine in biofilm eradication in vitro
No full textSuccessful treatment of skin infections requires eradication of biofilms found in up to 90 % of all chronic wounds, causing delayed healing and increased morbidity. We hypothesized that chitosan hydrogel boosts the activity of liposomally-associated membrane active antimicrobials (MAA) and could potentially improve bacterial and biofilm eradication. Therefore, liposomes (∼300 nm) bearing chlorhexidine (CHX; ∼50 μg/mg lipid) as a model MAA were incorporated into chitosan hydrogel. The novel CHX-liposomes-in-hydrogel formulation was optimized for skin therapy. It significantly inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced macrophage and almost completely reduced biofilm formation. Moreover, it reduced Staphylococcus aureus and Pseudomonas aeruginosa adherent bacterial cells in biofilm by 64.2–98.1 %. Chitosan hydrogel boosted the anti-inflammatory and antimicrobial properties of CHX
sj-pdf-1-inq-10.1177_00469580221082783 – Supplemental Material for Knowledge, practice and psychological symptoms among medical laboratory staff during COVID-19 pandemic in Nepal: An online based survey
No full textSupplemental Material, sj-pdf-1-inq-10.1177_00469580221082783 for Knowledge, practice and psychological symptoms among medical laboratory staff during COVID-19 pandemic in Nepal: An online based survey by Buddha Bahadur Basnet, Deepa Satyal, Roshan Pandit, Til Bahadur Basnet, Sandeep Khattri and Shyam Kumar Mishra in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p
Utilizing liposomal quercetin and gallic acid in localized treatment of vaginal Candida infections
No full textVulvovaginal candidiasis (VVC) is a widely spread fungal infection that causes itching, pain and inflammation at the vaginal site. Although common, currently available treatment suffers from limited efficacy and high recurrence. In addition, the growing problem of resistance to azole drugs used in current treatments emphasizes the need for superior treatment options. Antimicrobial polyphenols are an attractive approach offering multitargeting therapy. We aimed to develop novel liposomes for simultaneous delivery of two polyphenols (quercetin, Q, and gallic acid, GA) that, when released within the vaginal cavity, act in synergy to eradicate infection while alleviating the symptoms of VVC. Q was selected for its anti-itching and anti-inflammatory properties, while GA for its reported activity against Candida. Novel liposomes containing only Q (LP-Q), only GA (LP-GA) or both polyphenols (LP-Q+GA) were in the size range around 200 nm. Q was efficiently entrapped in both LP-Q and in LP-Q+GA (85%) while the entrapment of GA was higher in LP-Q+GA (30%) than in LP-GA (25%). Liposomes, especially LP-Q+GA, promoted sustained release of both polyphenols. Q and GA acted in synergy, increasing the antioxidant activities of a single polyphenol. Polyphenol-liposomes were not cytotoxic and displayed stronger anti-inflammatory effects than free polyphenols. Finally, LP-GA and LP-Q+GA considerably reduced C. albicans growth
Advanced topical delivery systems for membrane-active antimicrobials. Exploring nature to improve antimicrobial wound therapy
No full textCurrently, approximately 2% of the general population will experience at least one chronic wound throughout their lifetime. The numbers are expected to rise due to an aging population with a heightened disease burden. These wounds are major burdens for the patients; therefore, we need to find innovative approaches for bacterial eradication and improved wound treatment. We aimed to utilize nature’s toolbox to improve the effect of novel antimicrobial compounds, such as synthetic mimics of antimicrobial peptides (SMAMPs) and other membrane-active antimicrobials (MMAs), using pharmaceutical technology. In this project, we developed delivery systems based on liposomes and chitosan to improve anti-inflammatory, antimicrobial, anti-biofilm, and wound healing properties of novel SMAMPs. From the initial studies with the model compound chlorhexidine (CHX), liposomes-in-chitosan hydrogel was deemed the most suitable systems, and therefore selected for further development of delivery systems for two novel SMAMPs, namely 7e-SMAMP and 7a-SMAMP. From these studies, we confirmed that the 7e-SMAMP-liposomes and 7a-SMAMP incorporated in liposomes-in-chitosan hydrogel exhibited anti-inflammatory properties and a high level of biocompatibility. Furthermore, the anti-biofilm activities against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa of 7e-SMAMP improved upon its incorporation in liposomes and cell migration could be improved by incorporation of 7a-SMAMP in liposomes. Overall, the MAA-comprising liposomes-in-hydrogel systems proved to be suitable formulations with good biocompatibility and enhanced anti-inflammatory, antimicrobial, anti-biofilm, and wound healing properties. The novel delivery system comprising SMAMPs bears great potential as a platform in the therapeutic management of infected chronic skin wounds
Dental caries and preterm birth: a systematic review and meta-analysis
No full textObjectives: The primary objective of this systematic
review was to evaluate the association between dental
caries and preterm birth (PTB). The secondary objective
was ascertaining the difference between women with
dental caries who experienced PTB and those who did not
with regard to decayed, missing and filled teeth (DMFT),
and decayed, missing and filled surfaces (DMFS) indices.
Methods: MEDLINE, Embase, CINAHL and Cochrane
databases were searched initially in November 2015 and
repeated in December 2016. We included observational
cohort and case–control studies. Only studies reporting
the risk of PTB in women affected compared with those
not affected by dental caries in pregnancy were included.
Random-effect meta-analyses were used to compute the
summary OR of PTB among women with caries versus
women without caries, and the mean difference in either
DMFT or DMFS indices between women experiencing PTB
and those without PTB.
Results: Nine observational studies (4826 pregnancies)
were included. Women affected by dental caries during
pregnancy did not show a significantly higher risk of PTB
(OR: 1.16, 95%CI 0.90 to 1.49, P=0.25, I2
=35%). Also, the
women with PTB did not show significantly higher DMFT or
DMFS indices (summary mean differences: 1.56, P=0.10;
I
2
=92%and −0.15, P=0.9, I2
=89%, respectively).
Conclusion: Dental caries does not appear to be a
substantial risk factor for PT
Nanocarriers for tailored skin delivery: More than just the carriers?
No full textSkin diseases are among the top 5 most leading diseases causing non-fatal health burden worldwide and strategies to assure more effective treatments are urgently needed. Dermal therapy is very attractive due to the direct administration of the drug at the diseased skin site thus minimizing systemic side effects associated with the oral and parenteral routes. However, the great variety within the skin conditions can be a challenge in the development of effective dermal therapies. Based on the skin disease, the drug action is often required at different depths within the skin. The failure to penetrate the skin layers might result in sub-therapeutic drug levels at the targeted skin site and unsuccessful treatments. Phospholipid-based nanocarriers have great potential to overcome the current limitations in dermal therapy by assuring controlled and sustained drug delivery and promoting drug/substance transport in the deeper skin layers. The nanocarrier properties can be tailored and exploited to optimize skin drug delivery.
In the present study we optimized nanocarriers for tailored skin drug delivery. A closer-to-in vivo skin penetration model was developed to select nanocarriers with specific skin-targeted drug delivery potential. Deformable liposomes were found the most promising nanocarriers delivering model substances in the deeper skin layers while avoiding systemic absorption.
Further optimization of the selected nanocarrier was performed by exploring the effect of the liposomal surface charge on dermal delivery. The sustained skin penetration of drug/active substances for liposomally-associated drugs/substances was influenced by both the liposomal surface charge and physicochemical properties of the nanocarrier-associated drug/substance. The enhancement of the biological activities of both human epidermal growth factor and curcumin when incorporated in the liposomal system as compared to both active substances in solutions was found to be dependent on the liposomal surface charge.
Positively charged deformable liposomes embedded in chitosan hydrogel enabled stable bioadhesive hydrogel providing a sustained skin penetration of curcumin. The developed liposomal hydrogel formulation has a potential to be further evaluated as advanced wound dressing
Microscopy Meets Nanomedicine: The Challenge of Liposomes. Selecting, Understanding, and Adapting Imaging Techniques to Localize and Characterize Nanocarriers
No full textNanocarriers have brought several medical advances through better diagnostics and improved drug therapy. Yet, many promising preclinical findings were never translated into clinical success, consequently slowing drug development, and increasing its financial burden. By reliably predicting the nanoparticle fate at in vitro stages, the disappointment of suboptimal in vivo outcome could be avoided. To tackle the challenges of in vitro settings, this project aimed at gaining deeper insight on the interaction between nanocarriers and biological environment. Specifically, advance microscopy tools were used to visualize, characterize, and follow the biological fate of nanocarriers. As a back-to-basics approach, liposomes were chosen as model nanocarriers for their versatility, biocompatibility, and clinical relevance. When including a fluorescent molecule in the liposomal formulation, fluorescence dye and nanocarrier were found to affect each other’s properties in a manner dependent on environmental conditions (e.g., temperature, time, medium, and dye-specific chemistry). The fluctuations of fluorescence in the sample were further analyzed through image processing algorithms to obtain super resolution information from a diffraction-limited multi-frame acquisition. In parallel, to overcome some of the disadvantages often linked to the use of fluorescence, quantitative phase microscopy was optimized as a complementary label-free technique for the localization and characterization of liposomes in their hydrate state. Finally, fluorescence and label-free imaging were combined to determine the integrity of liposomes in nanofibers for topical administration. To understand the behavior of liposomes in cell culture, their internalization was followed using high throughput screenings, based on flow cytometry. These batch-mode results were validated in flow imaging and confocal microscopy. The behavior of liposomes, with and without PEG-coating, was compared in terms of intracellular localization and overall cellular response, resorting to the combination of fluorescence and label-free imaging (here, confocal and electron microscopy). Volumetric image correlation was then attempted, discussing benefits and limitations of the methods involved.Nanobærere har brakt med seg flere medisinske fordeler gjennom bedre diagnostikk og legemiddelterapi. Likevel er det mange prekliniske funn som aldri har blitt omsatt til klinisk suksess. Dette har resultert i langsommere legemiddelutvikling og økt finansiell byrde. Gjennom pålitelig bestemmelse av nanopartiklers skjebne under in vitro stadier kan man unngå skuffelsen av suboptimale in vivo resultater. For å håndtere utfordringene innenfor in vitro betingelser, sikter dette prosjektet på å oppnå dypere forståelse av interaksjonene mellom nanobærere og de biologiske omgivelsene. Her ble avanserte mikroskopiske verktøy brukt til å visualisere, karakterisere og følge den biologiske skjebnen til nanobærerne. Gjennom en tilnærming basert på grunnleggende prinsipper, ble liposomer valgt som modell for nanobærerne på grunn av deres allsidighet, biokompatibilitet og kliniske relevans. Når man inkluderte et fluorescerende molekyl i den liposomale formuleringen fant man ut at det fluorescerende fargestoffet og nanobæreren påvirket hverandres egenskaper på en måte som er avhengig av miljøforhold (f.eks. temperatur, tid, medium og kjemi spesifikt for fargestoffet). Fluktueringen av fluorescens i prøven ble videre analysert gjennom algoritmer for bildeprosessering for å oppnå informasjon om superoppløsning fra en diffraksjonsbegrenset datafangst gjennom flere billedtakninger. Parallelt, for å omgå noen av ulempene som ofte er knyttet opp mot bruk av fluorescens, ble kvantitativ fasemikroskopi optimalisert som en komplementær merkingsfri teknikk for lokalisering og karakterisering av liposomer i hydrert tilstand. Til slutt ble fluorescerende og merkingsfri billedtakning kombinert for å se på integriteten til liposomer i nanofibre laget for topikal administrasjon. For å forstå oppførselen til liposomer i cellekulturer ble deres internalisering fulgt gjennom screening av høyt volum, basert på flowcytometri. Disse resultatene ble validert gjennom flow imaging og konfokalmikroskopi. Oppførselen til liposomer, med og uten PEG-overtrekk, ble sammenlignet med hensyn til intracellulær lokalisering og total cellulær respons, gjennom en kombinasjon av fluorescens og merkingsfri billedtakning (konfokal og elektronmikroskopi). Volumetrisk bildekorrelasjon ble deretter utforsket gjennom drøfting av fordeler og begrensninger ved de involverte metodene
Surface modification of liposomes increases drug efficacy in local vaginal therapy
No full textThe vaginal inflammation and infection are one of the major female health issues, and unfortunately rather neglected. The anatomical structure and physiological conditions make vagina vulnerable to inflammation and infection, which if not successfully treated, can lead to deteriorating female health conditions. In pregnant patients, the pregnancy outcome can be severely affected. Although a standard treatment for vaginal infection is available, it is often not successful and recurrence rates are high. Therefore, a patientfocused drug development targeted at the vaginal inflammation and infection is the current social demand. Research and practice have shown that the topical treatment by the drugs against vaginal inflammation and infection can be superior comparing to the classical oral drug administration. However, the thick vaginal mucus lining the luminal surface of vagina and cervix, which protects the underlying tissue, limits the ability of a drug to reach vaginal mucosa. The success of mucosal delivery is highly dependent on a suitable drug carrier. Current dosage forms suffer from limited residence time at administration site and unpleasant leakage of dosage forms residues due to the self-cleansing action of the vagina, resulting in a reduced therapeutic effect. Therefore, liposomal drug delivery systems, with the ability to incorporate poorly soluble drugs and assure their stability, would be suitable for this purpose. Moreover, the modification of liposomal surface with mucoadhesive or mucoresistant polymers, might further enable improved mucosal drug delivery by providing prolonged residence time or rapid mucuspenetration, respectively.
We selected chitosan as a mucoadhesive polymer due to its biocompatibility, low toxicity and intrinsic anti-microbial potential. By combining the liposomal carrier and the mucoadhesive chitosan, an optimized vaginal drug delivery system with specific, prolonged and controlled drug release properties might be developed. Alternatively, improved drug delivery to vaginal mucosa can be provided through mucoresistant properties of the delivery system. Polyethylene glycol (PEG) plays an important role in this approach, and PEGylated liposomes enable controlled drug release in close proximity to the vaginal epithelium. Three model drugs/active ingredients were tested in mucoadhesive/mucoresistant liposomebased delivery systems, namely clotrimazole, resveratrol and interferon. Particularly interesting were the anti-oxidative and anti-inflammatory properties of resveratrol, which has a great potential in the treatment of vaginal inflammation and infection, however, its low solubility and poor bioavailability accompanied by poor stability limit its therapeutic effects. Liposomal system enhanced its activities and confirmed its potential.
The in vitro drug release and ex vivo penetration confirmed a sustained release of all liposomallyassociated drugs/active molecules. PEGylated liposomes (mucoresistant) assured improved penetration of interferon. By modulation of liposomal surface properties to be either mucoadhesive or mucoresistant it is possible to achieve prolonged residence time or deeper penetration of drug within vaginal epithelium, respectively. Moreover, the system can be modified for the different drugs, regardless of their molecular size and physicochemical characteristics
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