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1.
AAPS PharmSciTech ; 23(5): 136, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534759

RESUMO

The present work was to construct a roflumilast (ROF) cream for the treatment of psoriasis and clarify the dual roles of propylene glycol monocaprylate (PGM) in both molecular mobility of the cream, and drug-skin miscibility via drug-PGM-ceramide and drug-PGM-collagen intermolecular interaction. The cream formulation was screened through the stability study and in vitro skin administration study, optimized by Plackett-Burman and Box-Behnken design, and finally verified by the in vivo tissue distribution study. PGM demonstrated a significant drug skin retention enhancement effect (Rmax in vivo = 19.5 µg/g). It increased the molecular mobility of the oil phase of the cream by decreasing the molecular interaction of oil molecules proven by the rheology study (Ec = 3.73 × 10-4 mJ·m-3). More importantly, because of the good stratum corneum (SC) compatibility (∆H = - 403.88 J/g), PGM promoted an orderly flow of SC lipids (X-ray scattering, ΔLPP = 1.18 nm) and entered the viable epidermis/dermis (VE/DE) in large quantities (RPGM = 1186 µg/g), acting as a bridge to connect the drug to collagen through two H-bonds (LengthH-bond = 2.846 Å and 3.313 Å), thus increasing the miscibility of drug and VE/DE significantly (∆H = - 310.10 J/g, Emix = 21.66 kcal/mol). In this study, a ROF cream was developed successfully and the effect of PGM on the skin retention was clarified at molecular level.


Assuntos
Aminopiridinas , Pele , Aminopiridinas/farmacologia , Benzamidas , Colágeno/farmacologia , Ciclopropanos , Preparações Farmacêuticas , Propilenoglicol/química , Propilenoglicóis , Creme para a Pele
2.
Appl Microbiol Biotechnol ; 106(8): 2937-2951, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35416488

RESUMO

Glycerol dehydratase (gdrAB-dhaB123) operon from Klebsiella pneumoniae and NADPH-dependent 1,3-propanediol oxidoreductase (yqhD) from Escherichia coli were stably integrated on the chromosomal DNA of E. coli under the control of the native-host ldhA and pflB constitutive promoters, respectively. The developed E. coli NSK015 (∆ldhA::gdrAB-dhaB123 ∆ackA::FRT ∆pflB::yqhD ∆frdABCD::cat-sacB) produced 1,3-propanediol (1,3-PDO) at the level of 36.8 g/L with a yield of 0.99 mol/mol of glycerol consumed when glucose was used as a co-substrate with glycerol. Co-substrate of glycerol and cassava starch was also utilized for 1,3-PDO production with the concentration and yield of 31.9 g/L and 0.84 mol/mol of glycerol respectively. This represents a work for efficient 1,3-PDO production in which the overexpression of heterologous genes on the E. coli host genome devoid of plasmid expression systems. Plasmids, antibiotics, IPTG, and rich nutrients were omitted during 1,3-PDO production. This may allow a further application of E. coli NSK015 for the efficient 1,3-PDO production in an economically industrial scale. KEY POINTS:  â€¢ gdrAB-dhaB123 and yqhD were overexpressed in E. coli devoid of a plasmid system • E. coli NSK015 produced a high yield of 1,3-PDO at 99% theoretical maximum • Cassava starch was alternatively used as substrate for economical 1,3-PDO production.


Assuntos
Escherichia coli , Glicerol , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação , Deleção de Genes , Glicerol/metabolismo , Propilenoglicol/metabolismo , Propilenoglicóis/metabolismo , Amido/metabolismo
3.
Langmuir ; 38(14): 4243-4249, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35352955

RESUMO

We describe an experimental technique for the production of foams comprised of bubbles in a continuous phase of balanced quantities of aqueous and oil phases. Initially, two highly stable foams are fabricated: one typically made from olive oil with bubbles stabilized using partially fluorinated particles and the other made from a mixture of water and propylene glycol with bubbles stabilized using partially hydrophobic particles. After a rough mixture is prepared, the final mixed foam is fabricated via spinning the components together; the spinning leads to the final foam being well-mixed and dry. Here the final mixed foams are presented in thin-film form. We show the locations and roles of the various components.


Assuntos
Propilenoglicol , Água , Aerossóis , Interações Hidrofóbicas e Hidrofílicas , Água/química
4.
Chembiochem ; 23(9): e202100694, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35229962

RESUMO

A classic example of an all-protein natural nano-bioreactor, the bacterial microcompartment is a prokaryotic organelle that confines enzymes in a small volume enveloped by an outer protein shell. These protein compartments metabolize specific organic molecules, allowing bacteria to survive in restricted nutrient environments. In this work, 1,2-propanediol utilization microcompartment (PduMCP) was used as a model to study the effect of molecular confinement on the stability and catalytic activity of native enzymes in the microcompartment. A combination of enzyme assays, spectroscopic techniques, binding assays, and computational analysis were used to evaluate the impact of the major shell protein PduBB' on the stability and activity of PduMCP's signature enzyme, dioldehydratase PduCDE. While free PduCDE shows ∼45 % reduction in its optimum activity (activity at 37 °C) when exposed to a temperature of 45 °C, it retains similar activity up to 50 °C when encapsulated within PduMCP. PduBB', a major component of the outer shell of PduMCP, preserves the catalytic efficiency of PduCDE under thermal stress and prevents temperature-induced unfolding and aggregation of PduCDE in vitro. We observed that while both PduB and PduB' interact with the enzyme with micromolar affinity, only the PduBB' combination influences its activity and stability, highlighting the importance of the unique PduBB' combination in the functioning of PduMCP.


Assuntos
Ensaios Enzimáticos , Propilenoglicol , Catálise , Células Procarióticas , Temperatura
5.
Transplant Cell Ther ; 28(5): 242-247, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35196581

RESUMO

Autologous hematopoietic cell transplantation (AHCT) remains a standard therapeutic option for patients with multiple myeloma (MM). Outcomes have improved for this patient group after first AHCT, with the use of novel agents in induction, as well as post-transplantation maintenance. High-dose melphalan remains the gold standard as the conditioning regimen for MM. Traditional melphalan is a lyophilized formulation that after reconstitution has insufficient chemical stability and water solubility, thus requiring the addition of propylene glycol to act as a cosolvent to improve these characteristics. After the reconstitution of melphalan with propylene glycol-containing solution, impurities can develop within 30 minutes, and if further dilution occurs, the potency of melphalan diminishes. Propylene glycol is associated with a spectrum of toxicities that can be dose limiting. Evomela is a propylene glycol-free melphalan (PGF-Mel) that at a high dose of 200 mg/2 (100 mg/m2/d for 2 days) is approved for conditioning before AHCT in MM patients. Once reconstituted by directly dissolving in saline solution, PGF-Mel solution can be stored in the vial for up to 1 hour at room temperature or for up to 24 hours at refrigerated temperature (2° to 8°C) with no significant degradation. The demonstrated stability, up to 24 hours at room temperature, results in reduced handling requirements and increased convenience and flexibility of administration. Since its approval, Evomela has been the subject of several retrospective and investigator-initiated studies. This review summarizes the prospective and real-world evidence on practical aspects of PGF-Mel and critically appraises the available data and its clinical implications.


Assuntos
Amiloidose , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Amiloidose/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Propilenoglicol/uso terapêutico , Estudos Prospectivos , Prostaglandinas F/uso terapêutico , Estudos Retrospectivos
6.
J Control Release ; 343: 755-764, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35150813

RESUMO

The skin provides an attractive alternative to the conventional drug administration routes. Still, it comes with challenges as the upper layer of the skin, the stratum corneum (SC), provides an efficient barrier against permeation of most compounds. One way to overcome the skin barrier is to apply chemical permeation enhancers, which can modify the SC structure. In this paper, we investigated the molecular effect of three different types of glycols in SC: dipropylene glycol (diPG), propylene glycol (PG), and butylene glycol (BG). The aim is to understand how these molecules influence the molecular mobility and structure of the SC components, and to relate the molecular effects to the efficiency of these molecules as permeation enhancers. We used complementary experimental techniques, including natural abundance 13C NMR spectroscopy and wide-angle X-ray diffraction to characterize the molecular consequences of these compounds at different doses in SC at 97% RH humidity and 32 °C. In addition, we study the permeation enhancing effects of the same glycols in comparable conditions using Raman spectroscopy. Based on the results from NMR, we conclude that all three glycols cause increased mobility in SC lipids, and that the addition of glycols has an effect on the keratin filaments in similar manner as Natural Moisturizing Factor (NMF). The highest mobility of both lipids and amino acids can be reached with BG, which is followed by PG. It is also shown that one reaches an apparent saturation level for all three chemicals in SC, after which increased addition of the compound does not lead to further increase in the mobility of SC lipids or protein components. The examination with Raman mapping show that BG and PG give a significant permeation enhancement as compared to SC without any added glycol at corresponding conditions. Finally, we observe a non-monotonic response in permeation enhancement with respect to the concentration of glycols, where the highest concentration does not give the highest permeation. This is explained by the dehydration effects at highest glycol concentrations. In summary, we find a good correlation between the molecular effects of glycols on the SC lipid and protein mobility, and macroscopic permeation enhances of the same molecules.


Assuntos
Epiderme , Glicóis , Epiderme/metabolismo , Glicóis/metabolismo , Glicóis/farmacologia , Lipídeos/química , Permeabilidade , Propilenoglicol/química , Pele/metabolismo
7.
Biomed Res Int ; 2022: 3549061, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35047632

RESUMO

Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.


Assuntos
Antineoplásicos , Portadores de Fármacos , Nanopartículas , Naftoquinonas , Propilenoglicol , Neoplasias da Próstata , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Emulsões , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Naftoquinonas/química , Naftoquinonas/farmacologia , Propilenoglicol/química , Propilenoglicol/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
8.
J Med Toxicol ; 18(2): 155-158, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35043364

RESUMO

INTRODUCTION: Severe metabolic acidosis with elevated anion and osmol gap is suggestive of toxic alcohol ingestion. The absence of detectable methanol or ethylene glycol in the serum could mean that metabolism is complete or that other hypotheses have to be considered. Ingestion of less common alcohol or alcoholic ketoacidosis should be investigated as illustrated by the present observation. CASE REPORT: A 46-year-old woman was admitted with altered consciousness in the Emergency Department. In the presence of a high anion gap (peak value 39 mEq/L) metabolic acidosis with mildly increased osmol gap (peak value 19 mOsm/kg), there was a high suspicion of toxic alcohol ingestion in an individual with alcohol use disorder (AUD). Serum arterial lactate concentration was particularly high at 27 mmol/L. Urinalysis failed to reveal the presence of ketone bodies or oxalate crystals. The results of the serum determination of ethanol, methanol, ethylene glycol, and isopropanol were obtained within 2 h and were negative. Due to the severity of lactic metabolic acidosis and the persisting suspicion of intoxication by a less common toxic alcohol, antidotal therapy with ethanol was initiated together with hemodialysis. Correction of lactic metabolic acidosis was obtained. Results of urinalysis obtained later revealed the presence not only of propylene glycol and D-lactate but also of significant concentrations of ß-hydroxybutyrate as a marker of alcoholic ketoacidosis. DISCUSSION: The combination of propylene glycol ingestion and alcoholic ketoacidosis may have contributed to the severity of lactic acidosis.


Assuntos
Acidose Láctica , Acidose , Cetose , Acidose/induzido quimicamente , Acidose/diagnóstico , Acidose/terapia , Acidose Láctica/induzido quimicamente , Acidose Láctica/diagnóstico , Acidose Láctica/terapia , Etanol , Etilenoglicol , Feminino , Humanos , Cetose/induzido quimicamente , Cetose/diagnóstico , Ácido Láctico , Metanol , Pessoa de Meia-Idade , Propilenoglicol
9.
Environ Sci Pollut Res Int ; 29(20): 30537-30547, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35000155

RESUMO

Propylene glycol (PG) is widely used in the foods, pharmaceuticals, oil industry, animal feed, cosmetics and other industries. Because of the existence of a chiral carbon center, PG forms R (Rectus)- and S (Sinister)-enantiomers. Currently, the toxicity study of its R-, S-enantiomers is still very scarce. In this study, we have assessed the developmental toxicity and neurotoxicity of the R-, S-, and RS-PG enantiomers in zebrafish larvae. We found that exposure to R-, S-, and RS-PG enantiomers did not significantly affect the basic developmental endpoints of embryos or larvae (i.e., embryonic movement, hatching, mortality, malformation, heartbeat, body length), indicating that R-, S-, and RS-PG exposures did not exhibit the basic developmental toxicity in zebrafish larvae. The toxicity of three enantiomers was lower than that of ethanol, and there was no significant difference between them. However, R-, S-, and RS-PG exposures with high doses could significantly change the eye diameter and locomotor activity of larval zebrafish, indicating that R-, S-, and RS-PG enantiomers of high doses could potentially exhibit the neurotoxicity and ocular developmental toxicity in zebrafish larvae. Therefore, the potential neurotoxicity and ocular developmental toxicity of R-, S-, and RS-PG enantiomers for infants and toddlers should be considered.


Assuntos
Síndromes Neurotóxicas , Poluentes Químicos da Água , Animais , Embrião não Mamífero , Humanos , Larva , Propilenoglicol , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
10.
J AOAC Int ; 105(1): 46-53, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-34648035

RESUMO

BACKGROUND: Currently, there is no validated and available method internationally to determine the contents of nicotine and aerosolizing agents, namely glycerol and propylene glycol, added onto the heatsticks for use in heated smoking devices. OBJECTIVE: To determine the concentrations of nicotine, propylene glycol, glycerol and triacetin in heated tobacco products (HTPs) which is essential to understanding their health effects on smokers as well as secondhand smokers. METHODS: A simple methodology was developed and validated to simultaneously determine nicotine, propylene glycol, glycerol, and triacetin concentrations present in heatsticks. The tobacco material was extracted with a mixture of methanol-acetonitrile (7 + 3, by volume) with 1,3-butanediol and n-heptadecane as internal standards and analyzed with gas chromatography with flame-ionization detection (GC-FID). RESULTS: Good linearity was achieved over the following concentration ranges: 0.1-1.0 mg/mL for nicotine, 0.03-2.0 mg/mL for propylene glycol, 0.5-10.0 mg/mL for glycerol, and 0.1-4.0 mg/mL triacetin, with a coefficient of determination ≥0.995. The limits of detection and quantification were 0.0009 and 0.003 mg/mL for nicotine, 0.02 and 0.02 mg/mL for propylene glycol, 0.03 and 0.09 mg/mL for glycerol, and 0.005 and 0.02 mg/mL for triacetin, respectively. Good recoveries were obtained for nicotine at 89.8-102.0%, propylene glycol at 95.5-102.5%, glycerol at 95.2-102.6%, and triacetin at 90.6-103.1%. CONCLUSION: This method provides an affordable and reliable technique for routine analysis of nicotine and aerosolizing chemicals present in HTPs which is necessary to assess their impact to public health. HIGHLIGHTS: Many gaps remain in research on HTPs, in particular, country levels information on the content of the products are limited. This article contains information on a newly developed method to simultaneously determine nicotine, propylene glycol, glycerol and triacetin present in the tobacco material and butts of heatsticks for HTPs.


Assuntos
Nicotina , Produtos do Tabaco , Cromatografia Gasosa , Glicerol/análise , Propilenoglicol/análise , Triacetina
11.
Am J Emerg Med ; 53: 286.e1-286.e3, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34602331

RESUMO

INTRODUCTION: Propylene glycol (PG) is usually considered safe, however, toxicity can develop with high doses or when used for prolonged periods of time. PG can be found in some medications as well as some food products. We report a case of likely PG toxicity that occurred after compulsive daily ingestion of large amounts of corn starch. CASE REPORT: Our patient initially presented to an outside hospital (OSH) via ambulance for altered mental status. Her mental status improved after her blood sugar of 25 was corrected. On admission to OSH Emergency Department her initial vital signs included a heart rate of 115 bpm, blood pressure 113/59 mm/hg, temperature 35.8C. Pertinent labs included: sodium 119 mEq/L, bicarbonate 9 mEq/L, anion gap 29 mEq/L, creatinine 2.5 mg/dL and lactic acid 20 mEq/L. On transfer to our hospital her repeat lactic acid was 20 mEq/L, osmolar gap was 20. Her PG level, which was drawn several hours after her initial presentation, was 11 mg/dL. Our patient noted that she ingested a 16 oz. package of corn starch mixed with baking soda approximately every 2 days. Given the concerns for PG she was underwent intermittent hemodialysis. PG and lactic acid levels improved, however, she ultimately died due to complications from her hospitalization. DISCUSSION: PG causes toxicity through metabolism to lactic acid. While there are small amounts in food products and medications, under the right circumstances, PG can accumulate and lead to significant toxicity.


Assuntos
Amido , Zea mays , Comportamento Compulsivo , Ingestão de Alimentos , Feminino , Humanos , Ácido Láctico , Propilenoglicol/toxicidade
12.
J Pharm Sci ; 111(2): 479-484, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599998

RESUMO

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3 ± 0.34 °C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.


Assuntos
Síndromes do Olho Seco , Tacrolimo , Animais , Síndromes do Olho Seco/tratamento farmacológico , Inflamação , Propilenoglicol , Coelhos , Lágrimas
13.
Bioresour Technol ; 346: 126410, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34838635

RESUMO

Diols are important platform chemicals with extensive industrial applications in biopolymer synthesis, cosmetics, and fuels. The increased dependence on non-renewable sources to meet the energy requirement of the population raised issues regarding fossil fuel depletion and environmental impacts. The utilization of biological methods for the synthesis of diols by utilizing renewable resources such as glycerol and agro-residual wastes gained attention worldwide because of its advantages. Among these, biotransformation of 1,3-propanediol (1,3-PDO) and 2,3-butanediol (2,3-BDO) were extensively studied and at present, these diols are produced commercially in large scale with high yield. Many important isomers of C2-C4 diols lack natural synthetic pathways and development of chassis strains for the synthesis can be accomplished by adopting synthetic biology approaches. This current review depicts an overall idea about the pathways involved in C2-C4 diol production, metabolic intervention strategies and technologies in recent years.


Assuntos
Álcoois , Butileno Glicóis , Glicerol , Engenharia Metabólica , Propilenoglicol , Biologia Sintética
14.
Sci Total Environ ; 816: 151637, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774961

RESUMO

Glycol ethers are organic solvents present in countless products for professional and domestic use. The main toxicological concerns are hematotoxicity, respiratory and reproductive toxicity. The general population can be exposed when using products containing one or several glycol ethers that evaporate or if sprayed, generate aerosols that can be inhaled. The rate at which glycol ethers enters blood following inhalation exposure are unknown in humans, and chemical risk assessors only rely on animal and in vitro toxicity studies. Propylene glycol monomethyl ether (PGME) and propylene glycol monobutyl ether (PGBE) are two examples of glycol ethers used worldwide. Our study aimed to provide human toxicokinetic data after inhalation exposure of low PGME and PGBE concentrations tested alone or in mixture. Healthy participants (n = 28) were exposed to 35 ppm (131 mg/m3) of PGME and 15 ppm (i.e., 83 mg/m3) of PGBE for 2 or 6 h. Blood was regularly collected during the exposure sessions. PGME and PGBE were immediately bioavailable in blood during exposure, and the mean absorption rates were up to 13 µg/L/min and 2.45 µg/L/min, respectively. Maximum mean blood concentration (Cmax) was 2.91 mg/L and 0.41 mg/L for PGME and PGBE. The cumulative internal doses over time (area under the curve, AUC) were 11 mg∗h/L and 1.81 mg∗h/L for PGME and PGBE. PGME and PGBE total blood uptake could possibly be higher in physically active individuals, such as workers. We recommend that glycol ethers present on the market undergo toxicological testing with the internal doses we found in our toxicokinetic study.


Assuntos
Éteres , Exposição por Inalação , Animais , Éteres/toxicidade , Humanos , Exposição por Inalação/análise , Propilenoglicol/toxicidade , Solventes , Toxicocinética
15.
Drug Deliv Transl Res ; 12(4): 805-815, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33886076

RESUMO

Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical properties of the molecule, amitriptyline is also a promising candidate for delivery as a topical analgesic. Here we report the dermal delivery of amitriptyline from a range of simple formulations. The first stage of the work required the conversion of amitriptyline hydrochloride to the free base form as confirmed by nuclear magnetic resonance (NMR). Distribution coefficient values were measured at pH 6, 6.5, 7, and 7.4. Solubility and stability of amitriptyline were assessed prior to conducting in vitro permeation and mass balance studies. The compound demonstrated instability in phosphate-buffered saline (PBS) dependent on pH. Volatile formulations comprising of isopropyl alcohol (IPA) and isopropyl myristate (IPM) or propylene glycol (PG) were evaluated in porcine skin under finite dose conditions. Compared with neat IPM, the IPM:IPA vehicles promoted 8-fold and 5-fold increases in the amount of amitriptyline that permeated at 24 h. Formulations containing PG also appear to be promising vehicles for dermal delivery of amitriptyline, typically delivering higher amounts of amitriptyline than the IPM:IPA vehicles. The results reported here suggest that further optimization of topical amitriptyline formulations should be pursued towards development of a product for clinical investigational studies.


Assuntos
Analgesia , Absorção Cutânea , Administração Cutânea , Amitriptilina/metabolismo , Analgésicos , Animais , Excipientes , Propilenoglicol/química , Pele/metabolismo , Suínos
16.
J Biophotonics ; 15(1): e202100202, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34476912

RESUMO

A spatially resolved multimodal spectroscopic device was used on a two-layered "hybrid" model made of ex vivo skin and fluorescent gel to investigate the effect of skin optical clearing on the depth sensitivity of optical spectroscopy. Time kinetics of fluorescence and diffuse reflectance spectra were acquired in four experimental conditions: with optical clearing agent (OCA) 1 made of polyethylene glycol 400 (PEG-400), propylene glycol and sucrose; with OCA 2 made of PEG-400 and dimethyl sulfoxide (DMSO); with saline solution as control and a "dry" condition. An increase in the gel fluorescence back reflected intensity was measured after optical clearing. Effect of OCA 2 turned out to be stronger than that of OCA 1, possibly due to DMSO impact on the stratum corneum keratin conformation. Complementary experimental results showed increased light transmittance through the skin and confirmed that the improvement in the depth sensitivity of the multimodal spectroscopic approach is related not only to the dehydration and refractive indices matching due to optical clearing, but also to the mechanical compression of tissues caused by the application of the spectroscopic probe.


Assuntos
Propilenoglicol , Pele , Epiderme , Humanos , Análise Espectral
17.
Arch Dis Child ; 107(1): 65-67, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34266877

RESUMO

BACKGROUND: High-flow nasal oxygen (HFNO) is frequently used in hospitals, producing droplets and aerosols that could transmit SARS-CoV-2. AIM: To determine if a headbox could reduce droplet and aerosol transmission from patients requiring HFNO. METHODS: The size and dispersion of propylene glycol (model for patient-derived infectious particles) was measured using a spectrometer and an infant mannequin receiving 10-50 L/min of HFNO using (1) no headbox, (2) open headbox, (3) headbox-blanket or (4) headbox with a high-efficiency particulate (HEP) filter covering the neck opening. RESULTS: All headbox set-ups reduced the dispersal of droplets and aerosols compared with no headbox. The headbox-blanket system increased aerosol dispersal compared with the open headbox. The fraction of aerosols retained in the headbox for HFNO of 10 and 50 L/min was, respectively, as follows: (1) open headbox: 82.4% and 42.2%; (2) headbox-blanket: 56.8% and 39.5%; (3) headbox-HEP filter: 99.9% and 99.9%. CONCLUSION: A HEP-filter modified headbox may serve as an effective droplet and aerosol barrier adjunct for the protection of staff caring for children receiving HFNO.


Assuntos
Roupas de Cama, Mesa e Banho , COVID-19/prevenção & controle , Tosse , Oxigênio/administração & dosagem , Equipamento de Proteção Individual , SARS-CoV-2 , Aerossóis , Cânula , Hospitais , Humanos , Lactente , Recém-Nascido , Manequins , Pediatria , Propilenoglicol
18.
Dermatitis ; 33(2): 135-143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34115664

RESUMO

BACKGROUND/OBJECTIVE: Both active and inactive ingredients in topical ophthalmic agents may cause allergic contact dermatitis. Here, we examined ingredients in prescription topical ophthalmic medications available in the United States. METHODS: A comprehensive list of topical ophthalmic medications was generated using AccessPharmacy. Categories included antiglaucoma, antibiotic, antibiotic/corticosteroid, corticosteroid, antiviral, antifungal, mydriatic, and miotic agents. For each formulation, ingredients were investigated using the National Institutes of Health US National Library of Medicine database and/or manufacturer websites. Counts and proportions were calculated for inactive ingredients, including those in the American Contact Dermatitis Society (ACDS) Core 90 Allergen Series. RESULTS: Two hundred sixty-four unique prescription ophthalmic medications met the inclusion criteria. The most common ACDS Core 90 allergen/cross-reactor inactive ingredient was benzalkonium chloride (68.1%, 180/264), followed by sorbates (11.7%, 31/264), parabens (6.8%, 18/264), sodium metabisulfite (3.8%, 10/264), propylene glycol (3.0%, 8/264), and lanolin (3.0%, 8/264). Approximately 21% (20.8%, 55/264) of products had no ACDS Core 90 allergens/cross-reactor inactive ingredients. The most common ACDS Core 90 allergen/cross-reactor active ingredients were aminoglycoside antibiotics, bacitracin/polymyxin B, and corticosteroids. Important non-ACDS Core 90 allergens included inactive ingredients, such as EDTA 28.0% and thimerosal 2.7%, as well as active ingredients, especially ß-blockers. CONCLUSIONS: Benzalkonium chloride, sodium metabisulfite, propylene glycol, and lanolin were common inactive ingredient allergens. Most ophthalmic categories had low allergen formulations available for patients with contact allergy.


Assuntos
Alérgenos , Dermatite Alérgica de Contato , Hipersensibilidade a Drogas , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Humanos , Lanolina/efeitos adversos , Oftalmologia , Testes do Emplastro , Prescrições , Propilenoglicol/efeitos adversos , Sulfitos/efeitos adversos , Estados Unidos
19.
Med J Aust ; 216(1): 27-32, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-34528266

RESUMO

OBJECTIVES: To assess the chemical composition of electronic cigarette liquids (e-liquids) sold in Australia, in both their fresh and aged forms. DESIGN, SETTING: Gas chromatography-mass spectrometry analysis of commercial e-liquids sold in Australia (online and physical stores). MAIN OUTCOME MEASURES: Chemical composition of 65 Australian e-liquids - excipients/solvents, flavouring chemicals, other known e-liquid constituents (including nicotine), and polycyclic aromatic hydrocarbons - before and after an accelerated ageing process that simulated the effects of vaping. RESULTS: The measured levels of propylene glycol and glycerol often diverged from those recorded on the e-liquid label. All e-liquids contained one or more potentially harmful chemicals, including benzaldehyde, menthol, trans-cinnamaldehyde, and polycyclic aromatic hydrocarbons. Nicotine or nicotyrine were detected in a small proportion of e-liquids at extremely low concentrations. CONCLUSIONS: Australian e-liquids contain a wide variety of chemicals for which information on inhalation toxicity is not available. Further analyses are required to assess the potential long term effects of e-cigarette use on health.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/normas , Rotulagem de Produtos/normas , Acroleína/análogos & derivados , Acroleína/análise , Acroleína/normas , Administração por Inalação , Austrália , Aromatizantes/análise , Aromatizantes/normas , Cromatografia Gasosa-Espectrometria de Massas , Nicotina/análise , Nicotina/normas , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/normas , Propilenoglicol/análise , Propilenoglicol/normas
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