The Spray-Dried Alginate/Gelatin Microparticles with Luliconazole as Mucoadhesive Drug Delivery System

Candida species are opportunistic fungi, which are primary causative agents of vulvovaginal candidiasis. The cure of candidiasis is difficult, lengthy, and associated with the fungi resistivity. Therefore, the research for novel active substances and unconventional drug delivery systems providing effective and safe treatment is still an active subject. Microparticles, as multicompartment dosage forms due to larger areas, provide short passage of drug diffusion, which might improve drug therapeutic efficiency. Sodium alginate is a natural polymer from a polysaccharide group, possessing swelling, mucoadhesive, and gelling properties. Gelatin A is a natural high-molecular-weight polypeptide obtained from porcine collagen. The purpose of this study was to prepare microparticles by the spray-drying of alginate/gelatin polyelectrolyte complex mixture, with a novel antifungal drug—luliconazole. In the next stage of research, the effect of gelatin presence on pharmaceutical properties of designed formulations was assessed. Interrelations among polymers were evaluated with thermal analysis and Fourier transform infrared spectroscopy. A valid aspect of this research was the in vitro antifungal activity estimation of designed microparticles using Candida species: C. albicans, C. krusei, and C. parapsilosis. It was shown that the gelatin addition affected the particles size, improved encapsulation efficiency and mucoadhesiveness, and prolonged the drug release. Moreover, gelatin addition to the formulations improved the antifungal effect against Candida species.This researchwas funded by Medical University of Bialystok grant SUB/2/DN/22/004/2215.Marta Szekalska: [email protected] Szekalska - Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, PolandMagdalena Wróblewska - Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, PolandAnna Czajkowska-Kośnik - Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, PolandKatarzyna Sosnowska - Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, PolandPaweł Misiak - Department of Polymers and Organic Synthesis, Faculty of Chemistry, University of Białystok, 15-245 Białystok, PolandAgnieszka Zofia Wilczewska - Department of Polymers and Organic Synthesis, Faculty of Chemistry, University of Białystok, 15-245 Białystok, PolandKatarzyna Winnicka - Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, PolandWillems, H.M.E.; Ahmed, S.S.; Liu, J.; Xu, Z.; Peters, B.M. 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The role of the physician in secondary prevention of melanoma through skin self-examination during melanoma follow-up care

Introduction (Chapter 1) presents an overview of the research literature on melanoma and its prevention. Melanoma is the fastest growing and most lethal cancer of the skin (Trask et al., 2001). Its incidence in North America continues to rise annually posing a threat to an increasing number of individuals (American Cancer Society, 2018a; Canadian Cancer Society's Advisory Committee on Cancer Statistics, 2017). Given this increase it is imperative to implement effective primary and secondary preventative strategies, especially for those at highest risk. Clinical care guidelines recommend Skin Self-Examination (SSE) as an essential part of the lifetime follow-up care for melanoma survivors, who are at high risk for recurrence and new primary tumours (Coit et al., 2009; National Comprehensive Cancer Network, 2018). Patient predictors of SSE include age, gender, income, educational attainment, patient self-efficacy, as well as patient education regarding SSE, among others (Carli et al., 2003; Coups, Manne, Stapleton, Tatum, & Goydos, 2016; Kasparian et al., 2012; Kasparian et al., 2010; Manne & Lessin, 2006; McLoone, Menzies, Meiser, Mann, & Kasparian, 2013; K. A. Miller et al., 2015; Robinson, Fisher, & Turrisi, 2002; Robinson, Rigel, & Amonette, 1998). Less is known about the role of the physician support for uptake and maintenance of SSE practice (Aitken et al., 2004; Manne et al., 2004; Manne & Lessin, 2006; Rat et al., 2014). Consequently, the present dissertation reports on research examining the role of the above-mentioned variables for SSE behaviour. First, Health Care Climate Questionnaire (HCCQ), a measure of patient perceptions of general physician support of patient autonomy, was translated from the original English to French (Williams, Freedman, & Deci, 1998; Williams, Grow, Freedman, Ryan, & Deci, 1996). Then, validation analyses of the 6-item version of the HCCQ were conducted. The results (reported in Chapter 2) indicate that the scale is valid for use with melanoma survivors in both languages. Second, an intervention educating participants on early signs of melanoma and how to detect it via SSE was presented in Chapter 3. Participants' self-efficacy for SSE increased by 23% following the intervention and the improvements were retained at a three- and twelve-month follow-up. Analyses revealed that perceived physician support of SSE positively corresponded to the level of patient self-efficacy with higher patient-reported physician support being related to higher self-efficacy.Third, the relationship between the sociodemographic predictors of SSE (age, gender, income and education), physician support of SSE, self-efficacy and the practice of skin self-exams was further elucidated in Chapter 4. The level of SSE-specific self-efficacy was found to partially mediate the association between physician support of SSE and SSE behaviour after accounting for the only significant sociodemographic correlate of SSE in the current sample, i.e., education. Overall, the findings presented in the current dissertation suggest that educating patients about SSE and encouraging them to engage in it may have an impact on their confidence in the ability to perform effective self-exams. Moreover, physicians treating melanoma survivors may have a very important role to play in secondary prevention of this skin malignancy, not only through clinical exams but also through providing SSE-specific support to their patients, as per clinical care guidelines. The current research indicates that such support may not only increase patients' self-efficacy for this practice but also improve the practice of skin self-exams. The implications for research and practice are discussed in Chapter 5.Introduction (Chapitre 1) présente un survol de la littérature concernant le mélanome et sa prévention. Le mélanome est le cancer de la peau le plus létal et celui dont l'incidence a la croissance la plus rapide (Trask et al., 2001). Son incidence en Amérique du Nord continue d'augmenter annuellement et pose un risque à un nombre croissant d'individus (American Cancer Society, 2018a; Canadian Cancer Society's Advisory Committee on Cancer Statistics, 2017). Du a cette croissance il est impératif d'implémenter des stratégies de prévention efficaces. Les directives cliniques recommandent L'Auto-examen de la peau (AEP) comme un élément essentiel du calendrier de suivi des survivants du mélanome qui sont à haut risque de récurrence et de nouvelles tumeurs (Coit et al., 2009; National Comprehensive Cancer Network, 2018). Les prédicteurs de l'AEP incluent entre autres, l'âge, le genre, le salaire, l'accomplissement éducationnel, l'auto-efficacité du patient et aussi l'éducation du patient envers l'AEP (Carli et al., 2003; Coups et al., 2016; Kasparian et al., 2012; Kasparian et al., 2010; Manne & Lessin, 2006; McLoone et al., 2013; K. A. Miller et al., 2015; Robinson et al., 2002; Robinson et al., 1998).Peu de choses sont connues au sujet du rôle du support du médecin de la pratique de l'AEP (Aitken et al., 2004; Manne et al., 2004; Manne & Lessin, 2006; Rat et al., 2014). Conséquemment, la présente dissertation se rapporte à l'analyse et l'élucidation de la relation entre les variables mentionnées ci-haut dans la prédiction du comportement envers l'AEP. Premièrement, une traduction du Health Care Climate Questionnaire (HCCQ), une mesure de la perception du patient du support des médecins envers l'autonomie du patient, provenant de l'anglais original vers le français a été achevé (Williams, Freedman, et al., 1998; Williams et al., 1996). Par la suite, une analyse de validation de la version brève du HCCQ (6 items) a été effectué. Les résultats (rapporté au Chapitre 2) indiquent que cette mesure est valide et utile dans les deux langages.Deuxièmement, les résultats d'une intervention visant à éduquer les participants sur les signes précoces du mélanome et comment les détecter avec l'AEP ont été présenté au Chapitre 3. L'auto-efficacité des participants a augmenté de 23% suivant l'intervention et les améliorations ont été retenues lors des suivis de trois et douze mois. Des analyses ont révélé que la perception du support du médecins envers l'AEP correspond de façon positive envers le niveau d'auto-efficacité lorsqu'un niveau élevé de support du médecin envers l'AEP a été rapporté.Troisièmement, la relation entre les prédicteurs socio-démographiques de l'AEP (âge, genre, salaire et éducation), le support du médecin envers l'AEP, l'auto-efficacité et la pratique de l'AEP a été élucidé de façon plus approfondie au Chapitre 4. La médiation entre le support du médecin envers l'AEP et le comportement envers l'AEP par l'auto-efficacité spécifique à l'AEP a été démontré après avoir corrigé pour le seul facteur socio-démographique qui corrèle de façon significative dans le présent échantillon, i.e., l'éducation.Globalement, les résultats de la présente thèse suggèrent que l'éducation des patients envers l'AEP et de les encourager à s'y engager ont un impact sur leur confiance dans leurs habiletés à pratiquer un AEP. De plus, les médecins traitants les survivants du mélanome on possiblement un rôle très important à jouer dans la prévention secondaire de ce cancer, non seulement avec des examens cliniques (suivi standard pour le mélanome) mais aussi en fournissant un support spécifique à l'AEP à leurs patients, conformément aux directives cliniques. La présente recherche indique qu'un tel support augmente l'auto-efficacité de cette pratique et améliore l'AEP en soi. Les implications pour la recherche et pour la pratique clinique sont discutées au Chapitre 5

Validation of the English and French versions of the Brief Health Care Climate Questionnaire

Patient autonomy is a central value in medicine and critical component of adherence to medical advice. This article reports on a validation of the 6-item version of the Health Care Climate Questionnaire (HCCQ), a measure of autonomy support in health care settings, in a sample of 242 melanoma patients. The HCCQ showed excellent internal consistency ( α  = .91), structural validity (Tucker–Lewis index = .99; comparative fit index = .99; root mean square error of approximation = .06, 90 per cent confidence interval (.00, .11); standardized root mean square residual = .02; χ 2 (8, N  = 235) = 13.99, p  = .08) and construct validity (92.31% of hypothesized correlations with other measures confirmed). Acceptable 3-month test–retest reliability was observed ( r  = .55, p  < .001; intraclass correlation coefficient ( A , 1) = .54, p  < .001). The French version was found equivalent to the English version

Validation of the English and French versions of the Brief Health Care Climate Questionnaire

Patient autonomy is a central value in medicine and critical component of adherence to medical advice. This article reports on a validation of the 6-item version of the Health Care Climate Questionnaire (HCCQ), a measure of autonomy support in health care settings, in a sample of 242 melanoma patients. The HCCQ showed excellent internal consistency ( α  = .91), structural validity (Tucker–Lewis index = .99; comparative fit index = .99; root mean square error of approximation = .06, 90 per cent confidence interval (.00, .11); standardized root mean square residual = .02; χ 2 (8, N  = 235) = 13.99, p  = .08) and construct validity (92.31% of hypothesized correlations with other measures confirmed). Acceptable 3-month test–retest reliability was observed ( r  = .55, p  < .001; intraclass correlation coefficient ( A , 1) = .54, p  < .001). The French version was found equivalent to the English version

The Spray-Dried Alginate/Gelatin Microparticles with Luliconazole as Mucoadhesive Drug Delivery System

Candida species are opportunistic fungi, which are primary causative agents of vulvovaginal candidiasis. The cure of candidiasis is difficult, lengthy, and associated with the fungi resistivity. Therefore, the research for novel active substances and unconventional drug delivery systems providing effective and safe treatment is still an active subject. Microparticles, as multicompartment dosage forms due to larger areas, provide short passage of drug diffusion, which might improve drug therapeutic efficiency. Sodium alginate is a natural polymer from a polysaccharide group, possessing swelling, mucoadhesive, and gelling properties. Gelatin A is a natural high-molecular-weight polypeptide obtained from porcine collagen. The purpose of this study was to prepare microparticles by the spray-drying of alginate/gelatin polyelectrolyte complex mixture, with a novel antifungal drug&mdash;luliconazole. In the next stage of research, the effect of gelatin presence on pharmaceutical properties of designed formulations was assessed. Interrelations among polymers were evaluated with thermal analysis and Fourier transform infrared spectroscopy. A valid aspect of this research was the in vitro antifungal activity estimation of designed microparticles using Candida species: C. albicans, C. krusei, and C. parapsilosis. It was shown that the gelatin addition affected the particles size, improved encapsulation efficiency and mucoadhesiveness, and prolonged the drug release. Moreover, gelatin addition to the formulations improved the antifungal effect against Candida species