Point of care ultrasound: a clinical decision support tool for COVID-19.

The COVID-19 global pandemic has overwhelmed health services with large numbers of patients presenting to hospital, requiring immediate triage and diagnosis. Complications include acute respiratory distress syndrome, myocarditis, septic shock, and multiple organ failure. Point of care ultrasound is recommended for critical care triage and monitoring in COVID-19 by specialist critical care societies, however current guidance has mainly been published in webinar format, not a comprehensive review. Important limitations of point of care ultrasound include inter-rater variability and subjectivity in interpretation of imaging findings, as well as infection control concerns. A practical approach to clinical integration of point of care ultrasound findings in COVID-19 patients is presented to enhance consistency in critical care decision making, and relevant infection control guidelines and operator precautions are discussed, based on a narrative review of the literature.

The effects of gel-based manicure on pulse oximetry.

INTRODUCTION: Pulse oximetry is the standard monitoring technique of functional oxygen saturation (SpO2). As the use of fingernail polish has been described to alter SpO2 readings, its removal is commonly recommended prior to measurement. Gel-based manicures have gained popularity in recent years due to their attractiveness and longevity. However, the removal of gel nail polish requires a specialised procedure. Valuable time and resources can be saved if removal can be avoided. To our knowledge, there are no available studies on the effect of gel-based manicures on pulse oximetry readings. Hence, we evaluated the effect with two oximeters, using different technology and wavelength combinations. METHODS: 17 healthy female adult volunteers were recruited for this single-blind randomised controlled trial. Subjects with hypothermia, hypotension, poor plethysmographic waveform and nail pathology were excluded. Colours tested were: black, purple, navy blue, green, light blue, white, yellow, orange, pink and red. Pulse oximetry was measured at 15- and 30-second intervals using two different pulse oximeters, the Philips M1191BL and Masimo SET®. Means were compared using paired t-tests. RESULTS: Using the Masimo oximeter, light blue (ΔM = 0.97% ± 0.96%; p = 0.001) and orange (ΔM = 0.76 ± 1.17%; p = 0.016) gel nail polish resulted in a statistically significant increase from baseline SpO2 readings. With the Philips oximeter, the limits of agreement ranged from 2% for pink to 17% for black, indicating imprecision. CONCLUSION: Gel-based manicures can result in overestimations of actual readings, delaying detection of hypoxaemia. Gel nail polish should be routinely removed or an alternative monitoring technique sought.

Lipid Vesicles for the Skin Delivery of Diclofenac: Cerosomes vs. Other Lipid Suspensions.

PURPOSE: Lipid suspensions as drug carriers, including conventional liposomes, ethosomes, transferosomes, proniosomes, niosomes, PEG-PPG-PEG niosomes and stratum corneum liposomes (cerosomes), were formulated and compared. METHODS: Lipid vesicles were formulated and assessed with regards to enhancement of skin permeation of diclofenac and stability profiles of the formulations. Formulation-induced changes of the biophysical structure of excised human skin were monitored using the Fourier transform infrared spectroscopy. RESULTS: The stability profiles of these suspensions over 12 weeks did not show any significant drug leakage from the vesicles of interest (p > 0.05). FTIR observations indicated that the vesicles increased stratum corneum (SC) lipid fluidization and altered protein conformation. Skin permeability experiments showed that the free unencapsulated drug in the cerosomal formulations caused significant increase in drug permeation across the skin (p < 0.01). Low skin permeability of drug from the other lipid suspensions could be due to the entrapment of diclofenac within these vesicles which decreased the solubility of the hydrophilic drug in the skin lipids and the partition coefficient of the drug from these vesicles into the SC. CONCLUSION: Optimal drug entrapment in vesicles or alteration of the skin structure may not necessarily enhance the permeation of hydrophilic drugs across the human skin. These lipid vesicles may be further developed into carriers of both hydrophilic and hydrophobic drugs for topical and transdermal delivery, respectively.

Development and characterization of skin permeation retardants and enhancers: a comparative study of levothyroxine-loaded PNIPAM, PLA, PLGA and EC microparticles.

Polymeric microparticles suitable for topical and transdermal delivery systems were studied using poly D,L lactide (PLA), poly D,L lactide co glycoside (PLGA), poly (N-isopropylacrylamide) (PNIPAM) and ethyl cellulose (EC). Drug encapsulation efficacy, microparticle stability and skin permeation studies of levothyroxine loaded microparticles were carried out using excised human skin, and the skin permeation pattern was observed using confocal laser scanning microscopy. It was found that ethyl cellulose microparticles had the highest drug encapsulation and minimal drug leakage during the 14 week storage period. The PNIPAM microparticles had the lowest drug encapsulation efficiency and a fast degradation rate. The PLGA microparticles exhibited a temperature dependent drug leakage. Permeation studies using a flow-through diffusion cell indicated that the polymer transition temperature (T(g)) may influence the skin permeation rate of levothyroxine. Polyesters (PLA and PLGA) and PNIPAM acted as a skin penetration retardant and caused skin accumulation of the drug. These microparticles have potential use in skin formulations containing sunscreens and other active ingredients that are meant to be concentrated on the skin surface. However, skin permeation was observed from EC microparticles, therefore such polymers may be used as carriers in transdermal formulations to help achieve therapeutic concentrations of the drug in the plasma.

Smart polymeric nanofibers for topical delivery of levothyroxine.

Topical administration of levothyroxine (T4) helps to reduces deposits of adipose tissue on skin. The question is whether topical application of T4 could lead to systemic effects. In the present study a series of nanofibrous membranes were electrospun into blends of poly vinyl alcohol (PVA) and poly-N-isopropylacrylamide (PNIPAM) to develop a sustained topical delivery of T4. The polymeric nanofiber mats were characterized by field emission scanning electron microscopy (FESEM) and fourier transform infrared (FTIR) spectroscopy. In vitro permeation of the drug from the polymeric nanofibers was studied using excised human skin and the permeation mechanism investigated using confocal microscopy. It was observed that polymeric nanofibers were able to sustain the penetration of T4 to the skin and help maintain the effective drug concentration in the skin layers for longer period of time. These formulations may have potential uses in topical skin products and can help to increase the accumulation of the active compound on the skin surface thus minimize the adverse side effects which may be caused by systemic absorption. This may result in great improvement in consumer compliance, avoid frequent dosing and enhance the therapeutic effectiveness.

Novel vitamin and gold-loaded nanofiber facial mask for topical delivery.

L-ascorbic acid has been widely used in cosmetic and dermatological products because of its ability to scavenge free radicals and destroy oxidizing agents. However, it is chemically unstable and can easily be oxidized. The current cosmetic facial masks available in the market are pre-moistened, which means that the aqueous fluid content of the mask may oxidize some of the unstable active ingredients such as ascorbic acid. This work presents an anti-wrinkle nanofiber face mask containing ascorbic acid, retinoic acid, gold nanoparticles, and collagen. This novel face mask will only be wetted when applied to the skin, thus enhancing product stability. Once moistened, the content of the mask will gradually dissolve and release the active ingredients and ensure maximum skin penetration. The high surface area-to-volume ratio of the nanofiber mask will ensure maximum contact with the skin surface and help to enhance the skin permeation to restore its healthy appearance. Electrospun fiber mats may provide an attractive alternative to the commercial facial cotton masks.

Surface tension and wettability in transdermal delivery: a study on the in-vitro permeation of haloperidol with cyclodextrin across human epidermis.

OBJECTIVES: The aim of this work was to study the effect of surface tension and contact angle on the permeation of haloperidol across human skin using cyclodextrin derivatives. METHODS: Surface tension and contact angle of randomly methylated beta-cyclodextrin (RM beta-CD) and hydroxypropyl beta-cyclodextrin (HP beta-CD) solutions were measured. Haloperidol solubility and molecular modelling were carried out using the two cyclodextrin derivatives. In-vitro skin permeation was carried out using human skin models. KEY FINDINGS: The highest increase in drug solubility was observed when the drug was in solution with pH 5 when compared to non-ionised solution, resulting in a 128-fold increase in the intrinsic solubility of the drug. Surface tension measurements indicate a surface-active effect for RM beta-CD and HP beta-CD. Contact angle measurements showed that vehicles with higher skin wettability increased the contact of the drug with the skin surface and therefore resulted in higher drug permeation across human epidermis. CONCLUSIONS: It is concluded that transdermal flux of a drug through the skin may be optimised by controlling surface tension, drug solubility and skin wettability.

Transdermal delivery of haloperidol by proniosomal formulations with non-ionic surfactants.

Proniosomal formulations with non-ionic surfactant were studied. The effect of hydrophilicity and hydrophobicity of one or two surfactants on drug solubility, proniosome surface structure and stability and skin permeation of haloperidol from different formulations were investigated. Haloperidol (HP) was entrapped in proniosomes with very high efficiency for all formulations. Stability studies performed at 4 degrees C and 25 degrees C for a period of 6 weeks did not reveal any significant drug leakage (p>0.05). Formulations with single surfactants were found to increase the skin permeation of HP more than formulations containing two surfactants. The number of carbons in the alkyl chain of the non-ionic surfactant influenced the in vitro permeation of HP though the epidermis and the skin permeation was increased with increase in hydrophilic-lipophilic balance (HLB) value of the surfactant. Interfacial tension and surfactant hydrophobicity appeared to be useful for elucidating mechanism of skin permeation and for comparing drug fluxes from different proniosomal formulations.

Limonene GP1/PG organogel as a vehicle in transdermal delivery of haloperidol.

Penetration enhancers are a classical means for improving transdermal drug delivery (TDD). Enhancers permeate into the skin and reversibly decrease the barrier resistance. Basically, our aim is to formulate a transdermal gel containing an appropriate enhancer for a controlled drug release. Terpenes, namely limonene, linalool and cineole, in propylene glycol (PG) were first investigated in vitro for their capacity to enhance the percutaneous release of an anti-psychotic drug, haloperidol (HP). Relative to oxygenated linalool and cineole, hydrocarbon limonene was more effective as a skin enhancer; it increased human skin permeability and decreased lag time. Limonene was thus incorporated in an organogel comprised of gelator GP1 and PG. This skin-friendly gel in a transdermal patch could act as a long-acting formulation that delivers HP at a sustained percutaneous rate. The microscopic framework of the organogel is a branched network of interlocking fibres. Varying the gelator content modulates the fibre density and gel stiffness, and presents different degrees of resistance to drug diffusion on the vehicle side. Rheological and permeation studies demonstrated that an increase in gelator concentration increased gel moduli and decreased drug flux simultaneously. The rheology of the gel matrix influenced drug release rate in a manner described by several experimentally-derived correlations.

Oxide terpenes as human skin penetration enhancers of haloperidol from ethanol and propylene glycol and their modes of action on stratum corneum.

In this study, two terpenes with the same functional group; limonene oxide and pinene oxide were used at 5% w/v concentration in 50% v/v ethanol and 100% v/v propylene glycol (PG) to enhance the in vitro permeation of haloperidol (HP) through the human epidermis (or stratum corneum, SC). The enhancement mechanism of terpenes from both solvents was elucidated with HP-SC binding studies, Fourier transform infrared spectroscopy and differential scanning calorimetry. The enhancement activity of these terpenes was higher in 50% v/v ethanol than in 100% v/v PG. These terpenes in 50% v/v ethanol were predicted to provide the required therapeutic plasma concentration and daily-permeated amounts of the drug. Limonene oxide showed higher enhancement in both solvents, which was attributed to its less bulky structure. The terpenes in both solvents did not increase the partition of HP. Instrumental studies showed that these terpenes in 50% v/v ethanol extracted the SC lipids, disrupted the bilayer packing and partially fluidised the lipids. Limonene oxide in 100% v/v PG possibly disrupted the lipid bilayer, whilst leaving the overall bilayer structure intact and pinene oxide in the same vehicle fluidised the lipids within the ordered environment. This study showed that the mode of interactions of terpenes with SC were different in two solvent systems.