Budesonide

布地奈德
  • 文章类型: Journal Article
    背景:显微镜结肠炎(MC)是结肠的一种炎症性疾病。迄今为止,炎症性眼病与MC之间的关系尚不清楚。
    目的:评估炎症性眼病(虹膜睫状体炎和上巩膜炎)是否是MC的危险因素。
    方法:我们利用ESPRESSO研究(瑞典数据库,包含1965年至2017年来自胃肠道的所有活检数据)在瑞典进行了一项全国匹配的病例对照研究。总的来说,我们确定了14,338例活检证实的MC患者(1981年至2017年诊断).MC患者进行匹配(按年龄,性别,县和出生年份)与普通人群中的68,753名对照,并比较了两组中先前的炎症性眼病(定义为上巩膜炎或虹膜睫状体炎的诊断)的发生情况。使用条件逻辑回归以匹配变量为条件计算多变量调整比值比(aOR)。
    结果:大多数MC患者为女性(71.9%),诊断为MC的中位年龄为63.3岁(四分位距(IQR)=50.7-72.6)。与对照组的614例(0.9%)相比,约225例(1.6%)MC患者的炎症性眼病记录较早。这些数字对应于MC患者的炎性眼病的aOR为1.77(95%CI=1.52-2.07)。与兄弟姐妹相比,MC中既往炎症性眼病的aOR为1.52(95%CI=1.17-1.98),用布地奈德治疗的患者,作为临床重大疾病的代表,对以前的炎症性眼病有较高的aOR。
    结论:炎症性眼病在随后被诊断为MC的患者中更为常见。我们的发现强调,这些疾病可能具有共同的原因和炎症途径,并且对胃肠病学家具有临床意义。眼科医生和全科医生。
    BACKGROUND: Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear.
    OBJECTIVE: To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC.
    METHODS: We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables.
    RESULTS: A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3 years (interquartile range (IQR) = 50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI = 1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI = 1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases.
    CONCLUSIONS: Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners.
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  • 文章类型: Case Reports
    延迟释放(DR)布地奈德已获得美国食品和药物管理局(FDA)的快速批准,可用于减少原发性IgA肾病(IgAN)患者的蛋白尿,这些患者有重大疾病进展风险。批准是基于临床试验,主要涉及估计肾小球滤过率(eGFR)大于30mL/min/1.73m2的患者。然而,DR布地奈德减少肾功能下降的疗效,尤其是eGFR小于30mL/min/1.73m2和蛋白尿小于1g/d的患者,尚不清楚。我们报告了一个43岁的男性,有长期的高血压病史和活检证实的IgAN,他经历了蛋白尿和血清肌酐的进行性增加。尽管有最大的支持性管理,但eGFR下降至28mL/min/1.73m2。布地奈德DR治疗后,在最近的测量中观察到蛋白尿有减少的趋势和eGFR的稳定.虽然初步数据表明DR布地奈德主要用于eGFR超过30mL/min/1.73m2的患者,但我们的病例证明了DR布地奈德在其目前批准的适应症之外的应用潜力。这强调了对慢性肾脏疾病晚期患者进行额外研究的必要性。
    Delayed-release (DR) budesonide received expedited approval from the US Food and Drug Administration (FDA) as a treatment for reducing proteinuria in individuals with primary IgA nephropathy (IgAN) who are at significant risk of disease progression. The approval was based on clinical trials primarily involving patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2. However, the efficacy of DR budesonide in reducing kidney function decline, especially in patients with an eGFR less than 30 mL/min/1.73 m2 and proteinuria less than 1 g/d, remains unclear. We report the case of a 43-year-old man with a long-term history of hypertension and biopsy-proven IgAN who experienced a progressive increase in proteinuria and serum creatinine, along with a decline in eGFR to 28 mL/min/1.73 m2 despite maximal supportive management. Following therapy with DR budesonide, a decreasing trend in proteinuria and a stabilization of eGFR were observed in the recent measurements. While initial data suggested the effectiveness of DR budesonide primarily in patients with an eGFR over 30 mL/min/1.73 m2, our case demonstrates the potential of DR budesonide for use in scenarios beyond its currently approved indications. This underscores the need for additional research on patients with advanced stages of chronic kidney disease.
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  • 文章类型: Case Reports
    Currently, there is an increase in the incidence of microscopic colitis. There are difficulties in diagnosing this disease due to the variability of histological signs, variability of morphological changes in the mucous membrane of the colon in different parts of the colon, and the combination in one patient of not only various forms of microscopic colitis, but also other intestinal diseases. The article describes the differential diagnosis, an example of its staging and successful treatment of various forms of microscopic colitis with budesonide (two clinical cases presented).
    В настоящее время наблюдается рост заболеваемости микроскопическими колитами. Существуют трудности в диагностике данного заболевания из-за непостоянства гистологических признаков, вариабельности морфологических изменений слизистой оболочки толстой кишки в различных ее отделах, сочетания у пациента не только различных форм микроскопических колитов, но и других заболеваний кишечника. В статье приводится описание дифференциального диагноза, примера его постановки и успешного лечения различных форм микроскопического колита будесонидом (представлены два клинических случая).
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  • 文章类型: Case Reports
    过敏性支气管肺曲霉病(ABPA)是对烟曲霉的超敏反应,发生在哮喘或囊性纤维化患者中。这里,我们报告了一例年轻女性支气管哮喘患者,她因劳累而出现呼吸困难。她被诊断为患有ABPA,并开始口服伊曲康唑,同时继续吸入长效β-2肾上腺素能激动剂和中等剂量吸入皮质类固醇(ICS)治疗哮喘。治疗开始三个月后,患者的呼吸困难有了显著改善.然而,她体重增加了,面部浮肿,增加面部毛发和大腿内侧条纹的发育,小腿和小腹。发现她的血清皮质醇水平受到抑制,因此诊断为医源性库欣综合征。我们的案例描述了ICS和口服伊曲康唑之间潜在的严重相互作用,ABPA患者中非常常见的治疗方法。
    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus that occurs in patients with asthma or cystic fibrosis. Here, we report a case of a young female with bronchial asthma who presented to our hospital with worsening breathlessness on exertion. She was diagnosed to have ABPA and was initiated on oral itraconazole while continuing inhaled long acting beta-2 adrenergic agonist and medium dose inhaled corticosteroid (ICS) for her asthma. Three months after initiation of therapy, the patient had significant improvement in breathlessness. However, she had weight gain, facial puffiness, increased facial hair and development of striae on her inner thighs, calf and lower abdomen. Her serum cortisol levels were found to be suppressed and hence a diagnosis of iatrogenic Cushing\'s syndrome was made. Our case describes the potentially serious interaction between ICS and oral itraconazole, a treatment very commonly prescribed in patients with ABPA.
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  • 文章类型: Case Reports
    背景:IgAN的最佳治疗方法仍存在争议。试验NEFIGAN和NEFIGARD已经证明TRF-布地奈德(Nefecon)有效和安全地减少成人的蛋白尿,导致FDA批准Nefecon治疗成人IgAN。在小儿IgAN中,病因治疗尚不存在,和主要的疗法仍然是RAAS抑制剂和口服类固醇。据我们所知,这是少数关于TRF-布地奈德治疗的儿科报告之一.
    一名13岁男孩因复发性大血尿和蛋白尿而接受肾活检,导致IgAN诊断(MEST-C评分M1-E1-S0-T0-C1)。入院时,血清肌酐和UPCR略有升高.进行了三次甲基强的松龙脉冲,其次是泼尼松和RAAS抑制剂治疗。然而,10个月后,巨大血尿变得恒定,UPCR增加。做了新的肾活检,显示硬化病变增加。泼尼松停药,并开始使用IBDTRF-布地奈德9mg/天的试验。一个月后,巨大血尿发作消失,UPCR减少,有稳定的肾功能.5个月后,由于早晨皮质醇水平降低和药物供应困难,我们开始每3个月用3毫克的TRF-布地奈德断奶,1年后完全退出。在此期间,巨大血尿的发作显著减少,UPCR和肾功能维持稳定。
    结论:我们的病例表明TRF-布地奈德可被认为是小儿IgAN的有效二线治疗,特别是当需要长期服用类固醇来控制活动性炎症时。然而,迫切需要进行儿科临床试验,以确定TRF-布地奈德的正确剂量和耐受性.
    The best treatment for IgAN is still debated. The trials NEFIGAN and NEFIGARD have demonstrated that TRF-budesonide (Nefecon) efficiently and safely reduced proteinuria in adults, leading to FDA approval of Nefecon for adult IgAN. In pediatric IgAN, an etiological treatment does not yet exist, and the main therapies remain RAAS inhibitors and oral steroids. To our knowledge, this is one of the few pediatric reports of TRF-budesonide therapy.
    A 13-year-old boy underwent a kidney biopsy for recurrent macrohematuria and proteinuria, resulting in an IgAN diagnosis (MEST-C score M1-E1-S0-T0-C1). At admission, serum creatinine and UPCR were slightly increased. Three methylprednisolone pulses were performed, followed by prednisone and RAAS inhibitors therapy. However, after 10 months, macrohematuria became constant, and UPCR increased. A new kidney biopsy was performed, showing an increase in sclerotic lesions. Prednisone was discontinued, and a trial with IBD TRF-budesonide 9 mg/day started. One month later, macrohematuria episodes disappeared and UPCR decreased, with a stable kidney function. After 5 months, due to a reduction in morning cortisol levels and difficulty in drug provisioning, we started to wean TRF-budesonide by 3 mg every 3 months, with complete withdrawal after 1 year. During this period, episodes of macrohematuria dramatically decreased, and UPCR and kidney function were maintained stable.
    Our case demonstrates that TRF-budesonide could be considered an effective second-line treatment in pediatric IgAN, particularly when a long course of steroids is necessary to control active inflammation. However, pediatric clinical trials to identify the correct dosage and tolerability of TRF-budesonide are urgently needed.
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  • 文章类型: Case Reports
    背景技术系统性IgG4相关疾病是一种罕见的疾病,其可影响肝胆系统并可导致组织纤维化和器官衰竭。IgG4相关疾病的诊断标准已经确立,和全身性糖皮质激素建议开始治疗。除了糖皮质激素的有益性质,全身性类固醇的长期治疗具有毒性的风险,尤其是老年患者,其中IgG4相关疾病更常见。此外,在类固醇逐渐减少期间,疾病可能会复发。总的来说,维持治疗的最佳治疗方法尚未明确,这是当前临床研究的一个领域。病例报告我们介绍了1例IgG4相关硬化性胆管炎和组织学证实的全身性(多器官)IgG4相关疾病的患者,其疾病复发风险增加。免疫抑制剂(泼尼松龙,6-巯基嘌呤,布地奈德)对临床症状,实验室参数(AST,ALT,AP,γGT,胆红素),和影像学检查(磁共振胆管造影)记录超过56个月.在没有全身性泼尼松龙的情况下,使用局部作用的糖皮质激素布地奈德与低剂量6-巯基嘌呤联合使用,可以控制IgG4相关的硬化性胆管炎。在用6-巯基嘌呤治疗期间,发生了短暂的肝毒性,通过间歇性暂停和随后的剂量减少而逆转。此外,坏疽性胆囊炎是免疫抑制的并发症,并通过紧急胆囊切除术治疗。结论布地奈德可能是IgG4相关硬化性胆管炎的一种新的治疗方式。免疫球蛋白G4相关疾病的全身表现可以用低剂量6-巯基嘌呤控制。坏疽性胆囊炎可能是免疫抑制治疗的并发症。
    BACKGROUND Systemic IgG4-related disease is a rare disease that can affect the hepatobiliary system and may lead to tissue fibrosis and organ failure. Diagnostic criteria for IgG4-related disease are well established, and systemic glucocorticoids are recommended for initiation of treatment. Besides the beneficial properties of glucocorticoids, the long-term treatment with systemic steroids carries the risk of toxicity, especially in elderly patients, in whom IgG4-related disease is more common. Furthermore, disease relapses may occur during the tapering of steroids. Overall, the optimal treatment approach for maintenance therapy has not been clarified yet and is an area of current clinical research. CASE REPORT We present a patient with IgG4-related sclerosing cholangitis and histologically confirmed systemic (multi-organ) IgG4-related disease who was at increased risk of disease recurrence. The effects of immunosuppressants (prednisolone, 6-mercaptopurine, budesonide) on clinical symptoms, laboratory parameters (AST, ALT, AP, γGT, bilirubin), and imaging examinations (magnetic resonance cholangiography) were documented over 56 months. Control of IgG4-related sclerosing cholangitis was achieved - without systemic prednisolone - with the locally acting glucocorticoid budesonide in combination with low-dose 6-mercaptopurine. During treatment with 6-mercaptopurine, transient hepatotoxicity occurred, which was reversed by intermittent pausing and subsequent dose reduction. In addition, gangrenous cholecystitis occurred as a complication of immunosuppression and was treated by emergency cholecystectomy. CONCLUSIONS Budesonide could be a new treatment modality for IgG4-related sclerosing cholangitis. Systemic manifestations of immunoglobulin G4-related disease can be controlled with low-dose 6-mercaptopurine. Gangrenous cholecystitis may occur as a complication of immunosuppressive treatment.
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  • 文章类型: Journal Article
    背景:嗜酸性粒细胞性胃肠炎是一种罕见的儿童炎症性疾病。然而,目前尚无治疗小儿嗜酸性粒细胞性胃肠炎的标准指南.
    目的:报告儿童嗜酸性粒细胞性胃肠炎的诊治经验。
    方法:2017年1月至2019年12月,共22例患儿被诊断为嗜酸性粒细胞性胃肠炎。
    结果:内镜检查显示十二指肠有嗜酸性粒细胞浸润[嗜酸性粒细胞平均数/高倍视野(HPF)=53.1±81.5],胃(嗜酸性粒细胞/HPF的平均数量=36.8±50.5),和末端回肠(平均嗜酸性粒细胞数/HPF=49.0±24.0)。所有18例低嗜酸性粒细胞浸润(<14%)的儿童对初始药物治疗反应良好,无复发。而4例嗜酸性粒细胞高浸润(>14%)患儿中的2例在初次甲基强的松龙/孟鲁司特治疗后复发。此外,嗜酸性粒细胞高浸润(>14%)的儿童在接受布地奈德/甲基强的松龙作为初始或复发治疗后,症状缓解和组织学缓解,无进一步复发.
    结论:甲基强的松龙/孟鲁司特仍然是低嗜酸性粒细胞浸润儿童的最佳治疗方法(<14%)。布地奈德可作为高嗜酸性粒细胞浸润(>14%)患儿的初始或复发治疗。
    BACKGROUND: Eosinophilic gastroenteritis is a rare inflammatory disorder in children. However, there is still no standard guideline in the treatment of pediatric eosinophilic gastroenteritis.
    OBJECTIVE: To report our experience with the diagnosis and treatment of children with eosinophilic gastroenteritis.
    METHODS: From January 2017 to December 2019, a total of 22 children were diagnosed with eosinophilic gastroenteritis.
    RESULTS: Endoscopic examination showed eosinophil infiltration in the duodenum [mean number of eosinophils/high-power field (HPF) = 53.1 ± 81.5], stomach (mean number of eosinophils/HPF = 36.8 ± 50.5), and terminal ileum (mean number of eosinophils/HPF = 49.0 ± 24.0). All 18 children with low eosinophil infiltration (< 14%) responded well to the initial drug treatment without relapse, while two of four children with high eosinophil infiltration (> 14%) relapsed after initial methylprednisolone/montelukast treatment. In addition, children with high eosinophil infiltration (> 14%) showed symptomatic relief and histological remission without further relapse after receiving budesonide/methylprednisolone as initial or relapse treatment.
    CONCLUSIONS: Methylprednisolone/montelukast is still the best treatment for children with low eosinophil infiltration (< 14%). Budesonide can be considered as the initial or relapse treatment for children with high eosinophil infiltration (> 14%).
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  • 文章类型: Case Reports
    背景:近年来免疫检查点抑制剂(ICPI)的引入改变了许多肿瘤的自然病程。然而,接受这些药物治疗的患者可能出现免疫介导的不良事件;管理包括暂时或永久停止治疗和皮质类固醇,偶尔与其他免疫调节剂联合使用。这种免疫抑制,然而,也有许多不良事件,即使它在控制毒性方面是有效的,它延迟了免疫疗法的重新启动,因为目前的证据要求在再次攻击前将剂量逐渐减少至相当于≤10mg泼尼松龙。肠溶布地奈德是一种主要作用于肠道和肝脏的皮质类固醇制剂,由于其广泛的首过肝代谢。
    方法:一名76岁女性接受伊匹单抗治疗转移性黑色素瘤伴腹痛,呕吐,和腹泻至少前4天。实验室测试,其中,显示转氨酶和C反应蛋白升高。住院期间,病人也出现发烧。
    方法:患者,在排除转氨酶升高的替代原因后,被诊断为3级ipilimumab相关肝毒性。
    方法:布地奈德单药治疗;初始日剂量为12mg。
    结果:首次服用布地奈德后发热消退。首次服用布地奈德后约1个月,氨基转移酶恢复正常-接近正常。在这之后,每日剂量每2周减少3毫克,没有临床或生化复发。
    结论:该ICPI肝炎病例为,根据我们的知识,文献中第一个用布地奈德单药治疗。因此,布地奈德可能是治疗ICPI相关肝损伤的潜在有吸引力的选择,因为它的安全性和在选定的患者中更快的免疫疗法重新激发的潜在优势,而不需要剂量逐渐减少。与全身作用的皮质类固醇相反。将来应该进行临床试验,以验证或反驳这些发现。
    BACKGROUND: The introduction of immune-checkpoint inhibitors (ICPI) in recent years has changed the natural course of many neoplasms. However, patients receiving these medications may present immune-mediated adverse events; management includes temporary or permanent cessation of treatment and corticosteroids, occasionally combined with other immunomodulators. Such immunosuppression, however, also has numerous adverse events and even if it is effective in controlling toxicity, it delays immunotherapy reinitiation, as current evidence requires dose tapering to ≤10 mg prednisolone equivalent before rechallenge. Enteric-coated budesonide is a corticosteroid formulation acting primarily to the intestine and liver, as a result of its extensive first-pass hepatic metabolism.
    METHODS: A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever.
    METHODS: The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity.
    METHODS: Budesonide monotherapy was administered; initial daily dose was 12 mg.
    RESULTS: Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse.
    CONCLUSIONS: This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.
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  • 文章类型: Journal Article
    UNASSIGNED: Pathophysiology-targeting treatments exist for aspirin-exacerbated respiratory disease (AERD) through aspirin desensitization and biologics, such as dupilumab. With increasing attention paid to these treatments, which may be associated with significant side effects and/or cost, there is little description of chronic rhinosinusitis with nasal polyps (CRSwNP) response to treatment with intranasal corticosteroids and saline irrigations in AERD.
    UNASSIGNED: To determine the effect of intranasal budesonide irrigations for the treatment of CRSwNP in AERD.
    UNASSIGNED: This is an observational study of 14 AERD patients presenting to a rhinology clinic for CRS who were treated with twice daily high volume, low pressure irrigations with 240 mL of saline to which a 0.5 mg/2 mL respule of budesonide was added. All participants completed a 22-item Sinonasal Outcome Test (SNOT-22) at enrollment and at follow up 1 to 6 months later. Polyp scores were also calculated at each time point.
    UNASSIGNED: SNOT-22 scores ranged from 26 to 98 (median: 40.5) at enrollment and 3 to 85 (median: 38.5) at follow-up. Polyp scores ranged from 2 to 6 (median: 4) at enrollment at 0 to 6 (median: 2) at follow-up. Over the treatment period, change in SNOT-22 score ranged from -38 to 16 (median: -18) and change in polyp score ranged from -2 to 0 (median: -0.5). Approximately 57% of participants experienced at least 1 minimal clinically important difference in SNOT-22 score and 21% of participants had a SNOT-22 score <20 at follow-up.
    UNASSIGNED: Medical management with intranasal corticosteroids and saline irrigations alone leads to significant improvement in sinonasal symptomatology in a subset of AERD.
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  • 文章类型: Journal Article
    固体脂质纳米粒(SLN)已广泛应用于多种给药途径,在药物控释方面具有突出的优势。SLN的释放受多种因素支配,其中SLN的粒径是一个关键的粒径。该项目的目的是探索药物释放曲线与SLN粒径之间的关系。通过热高压均质化(HPH)方法合成了SLN,布地奈德(BUD)作为模型药物,并得到粒径增大的BUD-SLN1-BUD-SLN4,即120、240、360和480nm。制备的SLN具有良好的封装效率,载药量,和稳定性。体外释放行为研究表明,BUD-SLN在Tris-Maleate(Tris-M)培养基中的累积释放量可以忽略不计,而在Tris-M加胰酶培养基或Tris-M-乙醇培养基中,服从Ritger-Peppas模型或一级动力学模型,分别。值得注意的是,SLN的释放行为在一定程度上与SLN的平均粒径有关,但当粒径分布的交叉程度较大时,相关性不明显。本研究为了解SLN的体外释放提供了新的思路,对新型纳米药物的研发具有一定的参考价值。
    Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1-BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.
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