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1.
Front Public Health ; 12: 1366612, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645445

RESUMO

Introduction: Burnout, resilience, and thriving significantly impact academics, particularly in health professions, where responsibilities are extensive. This study aimed to explore these constructs among academic health professionals, examining sociodemographic and work-related factors influencing these outcomes. Methods: A cross-sectional study was conducted among academic health professionals via web-based professional networks from August 2022 to February 2023. Validated tools were used, and descriptive and inferential statistics were applied. Results: 505 participants were included, predominantly female (63%), with a mean age of 38.15 ± 9.6 years. High burnout was reported by 10.9%, 13.7% experienced exhaustion, and 6.3% were disengaged. Resilience and thriving were moderate at 59.2 and 51.9%, respectively. Age correlated negatively with burnout (r = -0.131, p = 0.003) but positively with resilience (r = 0.178, p < 0.001). Females reported higher exhaustion (p = 0.014), while males showed greater resilience (p = 0.016). Instructors exhibited lower resilience compared to assistant professors (p < 0.001) and associate professors (p < 0.001). Those at public universities reported higher exhaustion than those at private universities (p < 0.001). Conclusion: Variable levels of burnout, resilience, and thriving were observed among academic health professionals, influenced by sociodemographic and work-related factors. Interventions targeting resilience and thriving may mitigate burnout risk and enhance engagement among academics in health professions.


Assuntos
Esgotamento Profissional , Pessoal de Saúde , Resiliência Psicológica , Humanos , Feminino , Masculino , Esgotamento Profissional/psicologia , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Inquéritos e Questionários , Internacionalidade
2.
JAC Antimicrob Resist ; 5(6): dlad117, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37965099

RESUMO

Background: Increased antimicrobial resistance patterns lead to limited options for antimicrobial agents, affecting patient health and increasing hospital costs. Objectives: To investigate the antimicrobial prescribing patterns at two district hospitals in Northern Ireland before and during the COVID-19 pandemic. Methods: A mixed prospective-retrospective study was designed to compare pre- and during pandemic antimicrobial prescribing data in both hospitals using a Global Point Prevalence Survey. Results: Of the 591 patients surveyed in both hospitals, 43.8% were treated with 402 antimicrobials. A total of 82.8% of antimicrobial prescriptions were for empirical treatment. No significant difference existed in numbers of patients treated or antimicrobials used before and during the pandemic. There was a slight decrease of 3.3% in the compliance rate with hospital antimicrobial guidelines during the pandemic when compared with the pre-pandemic year of 2019, when it was 69.5%. Treatment based on patients' biomarker data also slightly decreased from 83.5% pre-pandemic (2019) to 81.5% during the pandemic (2021). Conclusions: There was no overall significant impact of the pandemic on the antimicrobial prescribing patterns in either hospital when compared with the pre-pandemic findings. The antimicrobial stewardship programmes would appear to have played an important role in controlling antimicrobial consumption during the pandemic.

3.
Eur J Hosp Pharm ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37748843

RESUMO

BACKGROUND: Clinical pharmacy services face challenges in Austria due to limited implementation and acceptance, outdated legislation and a lack of guidelines and training, despite the evidence from global studies of the positive impact of clinical pharmacists on patient care. OBJECTIVES: First, to identify the necessary types of clinical pharmacy interventions required at a 360-bed hospital located in Austria. Second, to evaluate the extent to which physicians accept the suggestions made by clinical pharmacists. METHODS: Over a period of 27 months, a clinical pharmacist made a series of interventions, which were evaluated using a six-point clinical significance scale. To determine the inter-rater reliability, a subset of 25 interventions was assessed for their clinical significance by four independent internal medicine physicians. RESULTS: A total of 1064 interventions were made by the pharmacist. Clinical pharmacy input was deemed necessary for 986 out of 1364 (72.3%) patients, with an average of 1.08 interventions per patient. The prompt acceptance rate of these interventions by physicians was 83.5% (888/1064), while 12.9% (137/1064) were considered by physicians but not immediately acted upon. The average clinical significance intervention rating was 2.15. The inter-rater reliability agreement between the four MDs and between the four MDs and the pharmacist was classified as 'good' to 'moderate'. CONCLUSION: This study in a secondary care Austrian hospital demonstrates the requirement for clinical pharmacy services, which are highly valued by other healthcare professionals. The clinical pharmacist is a key member of the multidisciplinary ward team, playing a vital role in reducing drug-related problems and enhancing patient safety. This work should now be scaled and tested in other Austrian hospitals.

4.
JAC Antimicrob Resist ; 5(4): dlad084, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37465105

RESUMO

Background: Antimicrobial stewardship (AMS) is imperative in addressing the menace of antimicrobial resistance (AMR) in health systems. Commonwealth Partnerships for Antimicrobial Stewardship uses a health partnership model to establish AMS in Commonwealth countries. The Hospital of Kwame Nkrumah University of Science and Technology in partnership with Ulster University, Northern Ireland, undertook an AMS project from November 2021 to May 2022. We report on implementation of the AMS, its impact on antibiotic use and infections management at the University Hospital; Kumasi, Ghana. Methods: The Global-Point Prevalence Survey (PPS) protocol was used to assess antibiotics use at the hospital at baseline, midpoint and end of the project. Feedback on each PPS was given to the hospital to inform practice, behavioural change and improve antibiotic use. Results: Antibiotic use reduced from 65% at baseline to 59.7% at the end of the project. The rate of healthcare-associated infections also reduced from 17.5% at baseline to 6.5%. Use of antibiotics from the WHO Access group was 40% at baseline but increased to 50% at the endpoint. Watch antibiotics reduced from 60% to 50% from baseline. Culture and susceptibility requests increased from baseline of 111 total requests to 330 requests in the intervention period to inform antimicrobial therapy. Conclusion: The model AMS instituted improved antibiotic use and quality of antimicrobial therapy within the study period. Continuous staff education and training in AMS, and use of standard tools for assessment and application of local data to inform infections management will ensure sustenance and improvement in the gains made.

5.
Antibiotics (Basel) ; 12(6)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37370392

RESUMO

With the advancement of biomedical research into antimicrobial treatments for various diseases, the source and delivery of antibiotics have attracted attention. In periodontal diseases, antibiotics are integral in positive treatment outcomes; however, the use of antibiotics is with caution as the potential for the emergence of resistant strains is of concern. Over the years, conventional routes of drug administration have been proven to be effective for the treatment of PD, yet the problem of antibiotic resistance to conventional therapies continues to remain a setback in future treatments. Hydrogels fabricated from natural and synthetic polymers have been extensively applied in biomedical sciences for the delivery of potent biological compounds. These polymeric materials either have intrinsic antibacterial properties or serve as good carriers for the delivery of antibacterial agents. The biocompatibility, low toxicity and biodegradability of some hydrogels have favoured their consideration as prospective carriers for antibacterial drug delivery in PD. This article reviews PD and its antibiotic treatment options, the role of bacteria in PD and the potential of hydrogels as antibacterial agents and for antibiotic drug delivery in PD. Finally, potential challenges and future directions of hydrogels for use in PD treatment and diagnosis are also highlighted.

6.
Expert Opin Drug Deliv ; 20(4): 507-522, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36924328

RESUMO

INTRODUCTION: It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site. AREAS COVERED: In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant. EXPERT OPINION: Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.


Assuntos
Doenças Cardiovasculares , Stents Farmacológicos , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Preparações Farmacêuticas , Qualidade de Vida , Sistemas de Liberação de Medicamentos , Implantes de Medicamento
7.
Explor Res Clin Soc Pharm ; 8: 100187, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36277308

RESUMO

Background: The delivery of pharmaceutical care - and what that means - has been at the centre of many transformations of the pharmacy profession in the last century. Today, the exponential growth of pharmacies which provide pharmaceutical care exclusively online has placed increased scrutiny on the quality of the care they provide. Aim: As more patients are managed by remote pharmaceutical care (via medicines delivery services), we sought to critically evaluate this service to identify new research directions. Methods: The COnsolidated criteria for REporting Qualitative research and Standards for reporting qualitative research guideline provided the methodological framework throughout this process. Results: We reveal that although home delivery services ensure that many patients have access to their medicines, it may reduce time available to provide comprehensive pharmaceutical care, particularly in traditional brick-and-mortar pharmacies. Conclusion: We highlight a critical need for research in this area and suggest a variety of research directions: is remote pharmaceutical care a matter of convenience? Does remote pharmaceutical care help patients adhere to their medicines? How do digital health innovations impact care across patient demographics? What does comprehensive pharmaceutical care mean for patients?

8.
Integr Cancer Ther ; 21: 15347354221096766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35796303

RESUMO

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.


Assuntos
Canabinoides , Cannabis , Neoplasias , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Endocanabinoides , Humanos , Neoplasias/tratamento farmacológico , Receptores de Canabinoides , Microambiente Tumoral
9.
Diagnostics (Basel) ; 12(4)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35453967

RESUMO

The aim of this systemic review was to collate and analyze existing data from published literature sources to identify the current understanding of the role of epigenetic and biological biomarkers in periodontal disease and diagnostics. A comprehensive searching strategy was undertaken in Embase, Medline, The Dentistry and Oral Sciences and CINAHL databases. Grey literature searching strategies were also employed. Articles published in the English language between 2017−2020 were included. A total of 1014 studies were returned of which 15 studies were included. All included articles were cross-sectional, case−control studies. Relevant data were extracted according to various demographic and methodological factors including cohort size, oral biofluid sampled, number of examiners, smoking status and reported outcomes. A measure of the biomarker levels and corresponding significance were documented where possible. This review identified that exRNA has the greatest diagnostic potential, with four biomarkers (SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1) displaying sensitivity of >71% and specificity of 100% in the assessed samples (p < 0.001) for gingivitis. This work also identifies the need for a unified approach to future research to draw meaningful comparison. Further investigations are warranted to definitively validate exRNA data and for the development of an exRNA-specific point-of-care diagnostic test.

10.
Med Teach ; 44(3): 267-275, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34629024

RESUMO

PURPOSE: Idea density has been shown to influence comprehension time for text in various populations. This study aims to explore the influence of spoken idea density on attainment in young, healthy subjects using demographic characteristics. METHODS: Students watched two online lectures and answered 10 multiple choice questions on them. Students received one more idea dense (MID) and one less idea dense (LID) lecture on two different subjects. RESULTS: Seventy-five students completed the study achieving a higher median score after a less idea-dense lecture (LID = 7(3), MID = 6(3), p = 0.04). Artificial neural network models revealed the first language as the main predictor of exam performance. The odds ratio (OR) of obtaining ≥70% after a more idea-dense lecture was six-time higher for the first language versus second language English speakers (OR = 5.963, 95% CI 1.080-32.911, p = 0.041). The odds ratio was not significant when receiving a less dense lecture (OR = 2.298, 95% CI 0.635-8.315, p = 0.205). Second-language speakers benefited from receiving a lower idea density, achieving a 10.8% score increase from high to low density, versus a 3.2% increase obtained by first language speakers. CONCLUSIONS: The propositional idea density of lectures directly influences students' comprehension, and disproportionately for second language speakers; revealing the possibility of reduced spoken idea density in levelling the attainment differential between first and second language speakers.


Assuntos
Idioma , Estudantes , Estudos de Coortes , Humanos
11.
Drug Deliv Transl Res ; 12(4): 758-791, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33474709

RESUMO

Transdermal drug delivery systems have become an intriguing research topic in pharmaceutical technology area and one of the most frequently developed pharmaceutical products in global market. The use of these systems can overcome associated drawbacks of other delivery routes, such as oral and parenteral. The authors will review current trends, and future applications of transdermal technologies, with specific focus on providing a comprehensive understanding of transdermal drug delivery systems and enhancement strategies. This article will initially discuss each transdermal enhancement method used in the development of first-generation transdermal products. These methods include drug/vehicle interactions, vesicles and particles, stratum corneum modification, energy-driven methods and stratum corneum bypassing techniques. Through suitable design and implementation of active stratum corneum bypassing methods, notably microneedle technology, transdermal delivery systems have been shown to deliver both low and high molecular weight drugs. Microneedle technology platforms have proven themselves to be more versatile than other transdermal systems with opportunities for intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring. These have shown that microneedles have been a prospective strategy for improving transdermal delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos , Agulhas , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Preparações Farmacêuticas , Estudos Prospectivos , Pele
12.
Pharmaceutics ; 13(12)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34959459

RESUMO

Development of specific medical devices (MDs) is required to meet the healthcare needs of children and young people (CYP). In this context, MD development should address changes in growth and psychosocial maturation, physiology, and pathophysiology, and avoid inappropriate repurposing of adult technologies. Underpinning the development of MD for CYP is the need to ensure MD safety and effectiveness through pediatric MD-specific regulations. Contrary to current perceptions of limited market potential, the global pediatric healthcare market is expected to generate around USD 15,984 million by 2025. There are 1.8 billion young people in the world today; 40% of the global population is under 24, creating significant future healthcare market opportunities. This review highlights a number of technology areas that have led to successful pediatric MD, including 3D printing, advanced materials, drug delivery, and diagnostic imaging. To ensure the targeted development of MD for CYP, collaboration across multiple professional disciplines is required, facilitated by a platform to foster collaboration and drive innovation. The European Pediatric Translational Research Infrastructure (EPTRI) will be established as the European platform to support collaboration, including the life sciences industrial sector, to identify unmet needs in child health and support the development, adoption, and commercialization of pediatric MDs.

13.
Adv Healthc Mater ; 10(3): e2001256, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33314714

RESUMO

Microneedle (MN) patches consist of a hydrogel-forming MN array and a drug-containing reservoir. Drug-containing reservoirs documented in the literature include polymeric films and lyophilized wafers. While effective, both reservoir formulations are aqueous based, and so degradation can occur during formulation and drying for drugs inherently unstable in aqueous media. The preparation and characterization of novel, nonaqueous-based, directly compressed tablets (DCTs) for use in combination with hydrogel-forming MN arrays are described for the first time. In this work, a range of drug molecules are investigated. Precipitation of amoxicillin (AMX) and primaquine (PQ) in conventional hydrogel-forming MN arrays leads to use of poly(vinyl alcohol)-based MN arrays. Following in vitro permeation studies, in vivo pharmacokinetic studies are conducted in rats with MN patches containing AMX, levodopa/carbidopa (LD/CD), and levofloxacin (LVX). Therapeutically relevant concentrations of AMX (≥2 µg mL-1 ), LD (≥0.5 µg mL-1 ), and LVX (≥0.2 µg mL-1 ) are successfully achieved at 1, 2, and 1 h, respectively. Thus, the use of DCTs offers promise to expand the range of drug molecules that can be delivered transdermally using MN patches.


Assuntos
Hidrogéis , Agulhas , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos , Microinjeções , Ratos , Pele , Comprimidos
14.
Mol Pharm ; 17(9): 3353-3368, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32706591

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) can cause harmful and potentially deadly infections. Vancomycin remains the first-line antibiotic treatment for MRSA-derived infections. Nevertheless, as a peptide drug, it is poorly absorbed when administered orally because of its high molecular weight and low permeability in the gastrointestinal tract and is therefore administered intravenously for the treatment of systemic diseases. In order to circumvent some of the many drawbacks associated with intravenous injection, other routes of drug delivery should be investigated. One of the strategies which has been employed to enhance transdermal drug delivery is based on microarray patches (MAPs). This work, for the first time, describes successful transdermal delivery of vancomycin hydrochloride (VCL) using dissolving MAPs (DMAPs) and hydrogel-forming MAPs (HFMAPs). VCL was formulated into DMAPs and reservoirs [film dosage forms, lyophilized wafers, and compressed tablets (CSTs)] using excipients such as poly(vinyl pyrrolidone), poly(vinyl alcohol), sodium hyaluronate, d-sorbitol, and glycerol. In this study, HFMAPs were manufactured using aqueous blends containing poly(methylvinyl ether-co-maleic acid) cross-linked by esterification with poly(ethylene glycol). The VCL-loaded CSTs (60% w/w VCL) were the most promising reservoirs to be integrated with HFMAPs based on the physicochemical evaluations performed. Both HFMAPs and DMAPs successfully delivered VCL in ex vivo studies with the percentage of drug that permeated across the neonatal porcine skin recorded at 46.39 ± 8.04 and 7.99 ± 0.98%, respectively. In in vivo studies, the area under the plasma concentration time curve from time zero to infinity (AUC0-∞) values of 162.04 ± 61.84 and 61.01 ± 28.50 µg h/mL were achieved following the application of HFMAPs and DMAPs, respectively. In comparison, the AUC0-∞ of HFMAPs was significantly greater than that of the oral administration control group, which showed an AUC0-∞ of 30.50 ± 9.18 µg h/mL (p < 0.05). This work demonstrates that transdermal delivery of VCL is feasible using DMAPs and HFMAPs and could prove effective in the treatment of infectious diseases caused by MRSA, such as skin and soft tissue infections, lymphatic-related infections, and neonatal sepsis.


Assuntos
Polímeros/química , Pele/metabolismo , Vancomicina/química , Vancomicina/farmacocinética , Administração Cutânea , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/farmacocinética , Maleatos/química , Staphylococcus aureus Resistente à Meticilina , Microinjeções/métodos , Agulhas , Permeabilidade/efeitos dos fármacos , Polietilenoglicóis/química , Absorção Cutânea/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Suínos , Vancomicina/administração & dosagem
15.
J Pharm Biomed Anal ; 189: 113429, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32593850

RESUMO

Vancomycin (VCN) is an antibiotic used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-derived infections. As it has a relatively narrow therapeutic window, it is imperative to develop a sensitive and reliable analytical method for drug monitoring and pharmacokinetic purposes. In the present study, quick sample preparations and a sensitive high-performance liquid chromatography method using UV detection (HPLC-UV) have been developed and validated. The analytical method for detection and quantification of VCN in rat plasma, skin and lymph node samples was validated based on the Food and Drug Administration (FDA) and European Medicine Agency (EMEA) bioanalytical method validation guidelines. The optimised plasma sample preparation involved a simple protein precipitation step, with extraction recovery of 100.3 ±â€¯0.92 %. VCN in all biological matrices was analysed in a HPLC-UV system (215 nm) using a Cortecs® C18 column (4.6 × 150 mm, 2.7 µm particle size) fitted with a guard cartridge set at 20 °C. Reverse phase HPLC under gradient conditions, with mobile phase consisting of 20 mM phosphate buffer containing 0.5 % v/v of triethylamine and a mixture of methanol - acetonitrile (70:30, v/v), and runtime of 12 min/sample was employed. The calibration standards used for plasma ranged between 0.1-50 µg/ml, while in the skin and lymph node matrices, standards ranged between 0.05-50 µg/ml with correlation coefficients (R2) of ≥ 0.9995 for all matrices. The method was selective, sensitive, accurate and precise for detecting and quantifying VCN in the biological matrices used. The validated method was successfully utilised in the detection of VCN in a pharmacokinetic and organ biodistribution study carried out in rats following oral and IV bolus administration of the drug. This validated bioanalytical method offers a wide range of potential applications in clinical therapeutic drug monitoring, pharmacokinetics and toxicology.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Preparações Farmacêuticas , Animais , Cromatografia Líquida de Alta Pressão , Linfonodos , Ratos , Reprodutibilidade dos Testes , Distribuição Tecidual , Vancomicina
16.
J Control Release ; 322: 177-186, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32200001

RESUMO

Treatment resistant depression is, by definition, difficult to treat using standard therapeutic interventions. Recently, esketamine has been shown as a viable rescue treatment option in patients in depressive crisis states. However, IV administration is associated with a number of drawbacks and advanced delivery platforms could provide an alternative parenteral route of esketamine dosing in patients. Hydrogel-forming microneedle arrays facilitate transdermal delivery of drugs by penetrating the outer layer of the skins surface, absorbing interstitial skin fluid and swelling. This subsequently facilitates permeation of medicines into the dermal microcirculation. This paper outlines the in vitro formulation development for hydrogel-forming microneedle arrays containing esketamine. Analytical methods for the detection and quantitation of esketamine were developed and validated according to International Conference on Harmonisation standards. Hydrogel-forming microneedle arrays were fully characterised for their mechanical strength and skin insertion properties. Furthermore, a series of esketamine containing polymeric films and lyophilised reservoirs were assessed as drug reservoir candidates. Dissolution testing and content drug recovery was carried out, followed by permeation studies using 350 µm thick neonatal porcine skin in modified Franz cell apparatus. Lead reservoir candidates were selected based on measured physicochemical properties and brought forward for testing in female Sprague-Dawley rats. Plasma samples were analysed using reverse phase high performance liquid chromatography for esketamine. Both polymeric film and lyophilised reservoirs candidate patches achieved esketamine plasma concentrations higher than the target concentration of 0.15-0.3 µg/ml over 24 h. Mean plasma concentrations in rats, 24 h post-application of microneedle patches with drug reservoir F3 and LW3, were 0.260 µg/ml and 0.498 µg/ml, respectively. This developmental study highlights the potential success of hydrogel-forming microneedle arrays as a transdermal drug delivery platform for ESK and supports moving to in vivo tests in a larger animal model.


Assuntos
Hidrogéis , Agulhas , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Ketamina , Microinjeções , Ratos , Ratos Sprague-Dawley , Pele , Suínos
17.
J Photochem Photobiol B ; 205: 111846, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151785

RESUMO

Propolis has been reported to possess rich content of antioxidant compounds and may provide health benefits through oxidative stress reduction. Presently, the formulation activities used to enhance the drug delivery have been hampered due to inherently low aqueous solubility and poor transdermal permeation of the bioactive phenols and flavonoids. Here, we show, the formulation of propolis extract (PE) into phytosome delivery systems. The optimum antioxidant activity was attained through extraction process using 75% v/v ethanol. The phytosome was prepared using thin-layer hydration technique with l-α-Phosphatidylcholine as a phospholipid. Fourier transform infrared (FTIR) was used to investigate the occurrence of molecular interactions between formulation components. This innovative approach could encapsulate >40% of bioactive compounds in PE, namely caffeic acid, quercetin, and kaempferol. FTIR spectroscopy indicated new hydrogen bond formation, supporting successful phytosome formulation. The phytosomes enhanced the dissolution up to 4-folds of bioactive compounds in bio-mimicked release media, as well as improved penetrability and skin retention up to 6-folds of the three main compounds of propolis, when compared to non-encapsulated PE formulation. Importantly, the hydrogel containing phytosome showed a potential for UVA and UVB radiation absorption, indicated by the SPF values of higher than 15. To conclude, this work shows promising novel delivery approaches for PE in the treatment of organ injured stress oxidative and skin aging.


Assuntos
Antioxidantes , Portadores de Fármacos , Hidrogéis , Nanopartículas , Própole/química , Protetores contra Radiação , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Compostos de Bifenilo/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Flavonoides/administração & dosagem , Flavonoides/análise , Hidrogéis/administração & dosagem , Hidrogéis/química , Técnicas In Vitro , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Fenóis/administração & dosagem , Fenóis/análise , Picratos/química , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/química , Ratos Sprague-Dawley , Pele/metabolismo , Absorção Cutânea , Fator de Proteção Solar , Raios Ultravioleta
18.
Drug Deliv Transl Res ; 10(3): 690-705, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32103450

RESUMO

Hydrogel-forming microneedle array patches (MAPs) have been proposed as viable clinical tools for patient monitoring purposes, providing an alternative to traditional methods of sample acquisition, such as venepuncture and intradermal sampling. They are also undergoing investigation in the management of non-melanoma skin cancers. In contrast to drug or vaccine delivery, when only a small number of MAP applications would be required, hydrogel MAPs utilised for sampling purposes or for tumour eradication would necessitate regular, repeat applications. Therefore, the current study was designed to address one of the key translational aspects of MAP development, namely patient safety. We demonstrate, for the first time in human volunteers, that repeat MAP application and wear does not lead to prolonged skin reactions or prolonged disruption of skin barrier function. Importantly, concentrations of specific systemic biomarkers of inflammation (C-reactive protein (CRP); tumour necrosis factor-α (TNF-α)); infection (interleukin-1ß (IL-1ß); allergy (immunoglobulin E (IgE)) and immunity (immunoglobulin G (IgG)) were all recorded over the course of this fixed study period. No biomarker concentrations above the normal, documented adult ranges were recorded over the course of the study, indicating that no systemic reactions had been initiated in volunteers. Building upon the results of this study, which serve to highlight the safety of our hydrogel MAP, we are actively working towards CE marking of our MAP technology as a medical device.


Assuntos
Biomarcadores/análise , Microinjeções/instrumentação , Administração Cutânea , Adulto , Desenho de Equipamento , Feminino , Voluntários Saudáveis , Humanos , Hidrogéis , Masculino , Microinjeções/efeitos adversos , Agulhas , Adesivo Transdérmico/efeitos adversos
19.
ACS Appl Mater Interfaces ; 12(11): 12478-12488, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066234

RESUMO

Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.


Assuntos
Técnicas Eletroquímicas/métodos , Agulhas , Ovalbumina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Administração Cutânea , Animais , Células Cultivadas , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Células Dendríticas , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microinjeções/instrumentação , Nanopartículas/administração & dosagem , Nanopartículas/química , Ovalbumina/administração & dosagem , Ovalbumina/química , Ovalbumina/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética
20.
Int J Biol Macromol ; 146: 290-298, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883883

RESUMO

One specific technological advance in transdermal drug delivery is the development of dissolving microneedles (DMNs), which efficiently deliver therapeutics through a rapid dissolution of polymers after penetration into the skin. However, there is a limited range of water soluble, biodegradable polymers that can be used to manufacture DMN. Here, we report for the first time, the preparation and characterisation of a DMN system from the carbohydrate biopolymer, pullulan (PL). PL gels, of varying concentration, were studied for viscosity, film formation properties, and subsequently, microneedle formation. Model molecules and protein/peptide were loaded into PL DMN and characterised. The stability of model biomolecules, such as FITC-BSA and insulin, following DMN manufacture were assessed using circular dichroism. Ex-vivo porcine skin permeation studies using Franz diffusion cell apparatus for Flu-Na and FITC-BSA loaded PL-DMN were conducted. This study demonstrates that PL DMNs may serve as a promising tool for efficient transdermal drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Glucanos , Agulhas , Absorção Cutânea , Administração Cutânea , Animais , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacologia , Preparações Farmacêuticas , Soroalbumina Bovina/farmacologia , Suínos
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