UNIQUE ORAL DRUG DELIVERY SYSTEM

An oral drug delivery system using proteinoid microspheres is discussed with respect to itsunique dependence on pH. It has been found that certain drugs such as insulin and heparin canbe encapsulated in proteinoid spheres at stomach pH's (1--3). These spheres also dissemble atintestinal pH's (6--7) releasing the drug for absorption. Using this technique low molecularweight heparin and human growth hormone have been orally delivered successfully to severalanimal species. Future work has been proposed to study the interaction and binding of thespecific drugs with synthesized oligopeptides.

Preparation of Ionic Liquid Functionalized Silica Nanoparticles for Oral Drug Delivery

The objective of this study is to utilize the pH sensitivity of modified silica nanoparticles (SNIL) by imidazole-based ionic liquid for oral delivery of insulin. In the first time, the imidazole was covalently attached to the 3-trimethoxysily-lpropyl chloride with replacement of all the chlorine atoms. Then, a silica nanoparticle was modified by N-(3-trimeth-oxysilylpropyl) imidazole. The nanocapsule (NCIL) was achieved after the etching of the modified silica nanoparticle template with hydrofluoric acid. The nanoparticles connected through an ionic liquid-like network were characterized by FTIR and SEM. Insulin was entrapped in these carriers and the in vitro release profiles were established separately in both enzyme-free simulated gastric and intestinal fluids (SGF, pH 1) and (SIF, pH 7.4), respectively. When these drug-loaded nanoparticles was placed in physiological buffer solution (pH 7.4), a partial negative surface charge on the modified silica nanoparticle was generated due to the deprotonation of silanol groups, and the strong electrostatic repulsion triggered a sustained release of the loaded molecules.

Rational design of oral drugs targeting mucosa delivery with gut organoid platforms

Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads(i.e.,immunogens)against gastric damage.In this study,hollowed nanocarriers(NCs:silica nanospheres and gold nanocages)with poly-l-lysine(PLL)coating and mammalian orthoreovirus cell attachment proteinσ1 functionalization(NC-PLL-σ1)were explored as functional oral drug delivery vehicles(ODDVs).The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells(M-cells)mediated transcytosis(viaσ1-α2–3-linked sialic acids adherence)across gastrointestinal epithelia.PLL coating provided protection and slow-release of rhodamine 6 G(R6G),a model payload.The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro.When compared with other experimental groups,the fully functionalized ODDV system(with PLL-σ1)demonstrated two significant advantages:a significantly higher transport efficiency(198%over blank control at 48 h);and protection of payloads which led to both better transport efficiency and extended-release of payloads(61%over uncoated carriers at 48 h).In addition,it was shown that the M cell presence in intestinal organoid monolayers(modulated by Rank L stimulation)was a determining factor on the transport efficiency of the ODDVs:more M-cells(induced by higher Rank L)in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload(R6G).The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines.

The influence of the gut microbiota on the bioavailability of oral drugs

Due to its safety,convenience,low cost and good compliance,oral administration attracts lots of attention.However,the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract.One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs,influencing the drug transport process and altering some gastrointestinal properties.In this review,we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs,which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

A “cluster bomb” oral drug delivery system to sequentially overcome the multiple absorption barriers

Oral drugs have been widely used in clinical therapy, but their developments were severely limited by the side effects of drug exposure as well as the multiple biological barriers. In this study, we constructed a “cluster bomb” oral drug delivery system (DOX@PFeL@L100) with core-shell structure to overcome the complex absorption barriers. The inner core termed as “bomb” that contains a lot of ultra-small diameter Fe_(3)O_(4) nanoparticles (DOX@PFeL NPs) loaded with doxorubicin (DOX) and modified with l-valine, which can efficiently penetrate the epithelial cells via PePT1 receptor mediated endocytosis. The outer shell of this “cluster bomb” is a layer of pH-sensitive polymer (Eudragit®L100) that can be served as a pH-responsive switch and effectively control the “bomb” release in the intestinal microenvironment to improve the antitumor efficiency by the Fenton like reaction of DOX and Fe^(2+)/Fe^(3+). This study demonstrates that the “cluster comb” oral drug delivery system can sequentially overcome the multiple biological barriers, providing a safe and effective approach for tumor therapy.

Milk-derived exosomes exhibit versatile effects for improved oral drug delivery

As endogenous courier vesicles,exosomes play crucial roles in macromolecule transmission and intercellular communication.Therefore,exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few years.However,few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral administration.Additionally,the mechanisms underlying their biomimetic properties as oral delivery vehicles remain unknown.Herein,insulin-loaded milk-derived exosomes(EXO@INS)were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic rats.Surprisingly,EXO@INS(50 and 30 IU/kg)elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected insulin.Further mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake,pH adaptation during gastrointestinal transit,nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus penetration.This study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma(BCL)due to their reliable efficacy,manageable safety,high accessibility,and convenience for use.Still,no guidelines or consensus focusing on oral drug therapies for BCL is available.To provide a reference of oral agent-based treatment for mature BCL,a panel of experts from the Lymphocyte Disease Group,Chinese Society of Hematology,Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China,combined with the latest authoritative guidelines in the world and current research reports.This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients.With the deepening of research and the development of standardized clinical applications,oral medications will bring better treatment to BCL patients,enabling more patients to benefit from them.

Adapting liposomes for oral drug delivery

Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes,oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract,difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes.

大黄三味片治疗抗精神病药药物性便秘临床观察

目的探讨大黄三味片治疗抗精神病药药物性便秘的有效性和安全性。方法收集2020年7月至2022年12月沈阳市精神科卫生中心精神科病房符合抗精神病药药物性便秘诊断标准的120例患者,按照随机数字法分为治疗组和对照组,每组60例,治疗组予大黄三味片治疗,对照组予乳果糖口服溶液。观察两组患者治疗前后便秘症状积分,排便时间,腹痛评分(VAS),大便性状改善时间、停药7 d内排便次数及生活质量评分。结果两组治疗有效率对比无统计学差异(P>0.05);治疗组大便性状改善时间短于对照组、停药7 d的排便次数多于对照组(均P<0.05);治疗后,治疗组便秘症状评分、腹痛评分、排便时间低于对照组,生活质量评分高于对照组(均P<0.05)。结论大黄三味片治疗抗精神病药药物性便秘临床疗效确切,有效减轻患者痛苦,停药后疗效持久,两组患者均未见不良反应,安全有效。

儿童苔藓样肉芽肿性口炎1例报道及文献回顾

目的探讨口腔苔藓样损害的分类、临床表现、诊断、鉴别诊断及治疗,为临床提供参考。方法获得医院伦理审批及患者知情同意,报道1例儿童口腔苔藓样损害病例,结合文献对口腔苔藓样损害的诊疗进行回顾分析。结果患儿舌背反复破溃伴疼痛3年余,舌背大面积糜烂面,形状不规则,糜烂周围见珠光白色纹,左侧糜烂区伴组织增生,约1.5 cm×2.0 cm,质地韧,宽蒂。舌背白色网纹组织切取活检病理诊断为苔藓样损害;舌背增生物切除活检病理诊断为苔藓样损害伴肉芽肿性炎。根据患者口内损害特征、系统病史、用药史、组织病理学检查结果,最终诊断为苔藓样肉芽肿性口炎。文献回顾表明,口腔苔藓样损害病因不明,临床上需与口腔扁平苔藓、口腔苔藓样药物反应、口腔苔藓样接触性损害、慢性溃疡性口炎等疾病鉴别。临床上治疗口腔苔藓样损害以糖皮质激素的局部和/或全身使用为主。结论目前口腔苔藓样损害的分类和诊断仍无统一标准,主要依靠病史询问、临床表现和组织病理学检查结果,治疗方法主要为糖皮质激素的局部和/或全身使用。

多学科协作护理专案在日间结直肠癌患者院外口服化疗药中的应用

目的探讨结直肠癌患者接受护理专案干预后对提高口服化疗药服药依从性、强化自我效能的作用。方法选择2022年6月至2022年12月在我院接受药物化疗治疗的结直肠癌患者300例作为研究对象,按照计算机随机编号抽取结果进行分组,对照组(150例)患者实施常规模式护理;观察组(150例)患者开展护理专案模式护理,对两组患者护理前后口服化疗药物服药依从性予以评估,比较两组结果的统计学差异。另外分别评估两组患者护理前后自我效能及生活质量,分析评分变化趋势。结果两组患者实施护理前服药依从性各个方面评分组间对比无统计学差异(P>0.05),观察组患者通过护理专案干预后,服药依从性评分高于对照组(P<0.05)。另外,观察组患者自我效能评分、生活质量评分均高于对照组(P<0.05)。结论针对结直肠癌患者通过实施护理专案干预能够有效提高口服用药的依从性,强化患者自我管理效能,提高生活质量,值得运用推广。

口腔苔藓样药物反应的研究进展

口腔苔藓样药物反应(oral lichenoid drug reactions,OLDR)是特殊体质者使用特定药物后引起的口腔黏膜炎性反应,属于口腔苔藓样损害(oral lichenoid lesions,OLL)这一病种,其临床表现和病理表现与其他种类的OLL相比不存在明显的特异性,可能诱发OLDR的药物种类繁多,包括了降压药、非甾体抗炎药、降糖药、抗焦虑/精神类药物、生物制剂等,治疗方案除局部或全身使用糖皮质激素以外,停用可疑药物是最有效的治疗措施,大多数患者的黏膜溃疡、糜烂能得到较大缓解,但可能仍有白纹残留。虽然OLDR已在文献报道和临床工作中得到广泛关注,但由于缺乏系统的认识,对于OLDR的诊断并没有公认的标准,也缺乏规范化的诊疗流程,且相关药物与口腔苔藓样病变之间的因果关系仍然存在疑问。针对以上问题,笔者检索了近20年国内外药物相关口腔扁平苔藓和苔藓样损害的文献,其中绝大多数为病例报告,仅有少量病例对照研究。本文从相关概念、可疑药物、临床及病理表现、治疗预后4个方面介绍了其研究现状,希望能为相关苔藓样损害的预防、诊断和临床治疗提供理论参考。文献综述显示了该疾病在病因、发病机制、临床诊疗、治疗预后等方面仍有大量问题尚不明确,仍需进一步开展临床及基础研究予以深入探索。

司库奇尤单抗注射液致口腔苔藓样药物反应1例

1例57岁女性患者因银屑病给予司库奇尤单抗注射液治疗,第8次给药后舌背及左颊黏膜出现大面积网状白纹伴充血糜烂,给予糖皮质激素等治疗3周后好转,再次给药后症状加重,诊断为口腔苔藓样药物反应,给予糖皮质激素等治疗8周后好转。患者停用司库奇尤单抗注射液4个月后不良反应未复发。该病例的口腔苔藓样药物反应与司库奇尤单抗注射液的关联性评价为“肯定”,在国内尚未见文献报道。口腔苔藓样药物反应临床表现多为单侧颊黏膜白纹伴充血糜烂,停用可疑药物与局部应用皮质类固醇是目前治疗最有效的手段。

茶碱类药物在喘息性疾病中的应用进展

喘息性疾病指包括哮喘、慢性阻塞性肺疾病等临床以喘息为主要症状的一组疾病,在呼吸系统疾病中发病率较高。茶碱类药物作为临床常见的一类平喘药物,在抑制炎症反应、调节免疫、促进细胞凋亡、激活组蛋白脱乙酰酶等方面发挥作用。茶碱类药物种类繁多,主要有茶碱、氨茶碱、二羟丙茶碱和多索茶碱,且茶碱类药物价格低廉,在喘息性疾病的治疗上有确切的疗效。随着茶碱不同制剂的推出,选择合适的制剂既可以保持疗效,还能减少副作用的发生。未来将有更多疗效确切、价格低廉的茶碱类药物应用于临床。

国家集采背景下某院口服降糖药使用情况分析

目的探讨第二、第三、第四和第五批国家集中带量采购(以下简称“国家集采”)执行后对泉州市第一医院(以下简称“某院”)口服降糖药物的使用影响,拟为医院药事管理与临床用药提供优化建议。方法调取某院信息系统内各批国家集采实施前后一年口服降糖药的使用数据,统计其单价降幅、用药频度(DDDs)、药品使用金额、日均治疗费用(DDC)、同类药品使用占比、节省费用和节省费用率等指标,分析国家集采政策实施效果。结果国家集采执行后,各批次中选品种价格呈现不同程度的降低,大部分集采品种的DDC和使用金额均明显下降,其使用量和DDDs同比增加,药品费用节省金额为10.40万~284.49万元,费用节省率为18.79%~4340.88%。但部分同类可替代品种在集采执行后出现DDDs的增长。结论执行国家集采后,某院的口服降糖药品费用显著降低,切实减轻患者药品费用负担。而在执行集采过程中某院仍需优化集采药品及同类可替代药品的管理方案,以促进集采政策的进一步落实。

药师干预口服抗肿瘤药患者用药依从性的成效分析

目的评价药师干预口服抗肿瘤药物患者用药依从性的成效。方法采用计算机检索PubMed,Web of Science,Embase及中国知网、维普和万方医学数据库中药师对口服抗肿瘤药物患者用药依从性进行干预的相关研究,检索时限为自建库起至2022年4月1日。采用Cochrane偏倚风险评价工具RoB2进行偏倚风险评价,采用RevMan 5.4软件进行Meta分析,无法进行Meta分析的结局指标进行描述性统计。结果共纳入8项随机对照试验(RCT),涉及患者717例。常见的用药依从性干预措施为定期随访、用药教育和咨询。测量方法包括直接评估法和间接评估法,其中直接评估法通过测量血药浓度;间接评估法包括客观评估法(药片计数法和电子监测设备)和主观评估法(患者问卷调查)。4项以患者是否依从用药二分类变量为结局指标的RCT的Meta分析结果显示,药师对口服抗肿瘤药物患者进行药学干预可显著提高其用药依从性[OR=4.59,95%CI(1.09,19.29),P=0.04];亚组分析结果显示,采用主观评估法评估用药依从性的研究中,干预组的用药依从性显著提高[OR=6.84,95%CI(2.84,16.50),P<0.0001]。结论药师积极对口服抗肿瘤药物患者进行药学干预,可提高患者的用药依从性。

复方甘草口服溶液的应用现状及思考

目的 梳理复方甘草口服溶液监管现状并提出建议。方法 检索中国知网、万方数据、维普网、美国食品药品监督管理局、我国国家药品监督管理局及省级药品监督管理局网站有关文件,对纳入文献进行汇总和分析。结果 当前我国复方甘草口服溶液存在生产制备过程部分不稳定、含量测定标准相对不全面、说明书记载相对不全、药品不良反应临床表现多样等状况。结论 建议参考国内外对类似药物的监管办法优化对复方甘草口服溶液的监管措施;企业规范销售对象与流程;加强医务人员培训、开展科普活动。

牙龈卟啉单胞菌对口腔鳞状细胞癌化疗耐药行为的影响

目的:研究口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)肿瘤中牙龈卟啉单胞菌(Porphyromonas gingivalis,P.gingivalis)对OSCC化疗治疗过程中化疗耐药性的影响。方法:使用原位免疫杂交的方法检测67例OSCC患者肿瘤组织中P.gingivalis的含量,使用细胞计数试剂盒(cell counting kit-8,CCK8)实验检测OSCC细胞在P.gingivalis感染后化疗药物的细胞毒性作用,使用Western blot实验检测OSCC细胞在P.gingivalis感染后耐药蛋白的表达。结果:OSCC上皮组织中P.gingivalis含量比非肿瘤区域上皮组织中P.gingivalis含量高,P.gingivalis的感染降低了化疗药物紫杉醇对OSCC细胞的杀伤作用(P<0.05),在P.gingivalis感染后耐药蛋白P-糖蛋白在肿瘤细胞中的表达显著提高。结论:OSCC患者肿瘤组织中P.gingivalis含量较高,可能与OSCC化疗耐药相关。

《鼓励研发申报儿童药品清单》口服药品有效成分在某儿童专科医院住院患儿中药物剂型可接受性情况调查

目的 分析《鼓励研发申报儿童药品清单》中的口服药物成分在某三甲儿童专科医院不同年龄段患儿中的实际应用及该院目前配备剂型适宜性的情况。方法 从4批《鼓励研发申报儿童药品清单》中的口服液体制剂的有效成分中,选取某三级儿童专科医院目前有该活性成分的口服药物,分析2023年11月9日至2023年12月8日住院患儿使用这些药物的调剂频次及用药时的年龄。基于我国《儿童用药(化学药品)药学开发指导原则(试行)》提出的不同年龄段儿科人群用药可接受的剂型选择,针对不同年龄组(新生儿、婴幼儿、学龄前儿童、学龄儿童、青少年),评估各药物的剂型适宜性。结果 在2023年11月9日至2023年12月8日时间段内,该院住院患儿使用过含4批《鼓励研发申报儿童药品清单》中的口服液体制剂的有效成分的口服药物共14种。在14种药物(片剂或胶囊剂)的4542次调剂记录中,新生儿和婴幼儿均为剂型“不适宜”,分别为132次和1111次;此2个年龄段使用频次最高的药物为左甲状腺素钠片、螺内酯片、熊去氧胆酸胶囊。对于学龄前儿童,适宜程度为“适用但存在问题”的胶囊剂共992次,其余为可“适用但不优选”的片剂1327次;对于学龄儿童,均为“适用”;对于青少年,均为“最优选”。“不适宜”或“适用但存在问题”的用药次数占总次数的49.2%。对各药物的剂型适宜性得分计算加权平均,剂型适宜性最低的药物分别为左甲状腺素钠片、熊去氧胆酸胶囊、他克莫司胶囊。结论 《鼓励研发申报儿童药品清单》中的口服液体制剂对应的片剂或胶囊剂在该院新生儿和婴幼儿中均有一定的应用,且剂型适宜性较低。医疗机构应当进一步加强儿童用药遴选与配备。对于新生儿及婴幼儿,需要加急研发他们常用药物的剂型以及分剂量调配的相关规范。