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.

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.

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.

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.

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.

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.

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.

氧化石墨烯在口腔种植修复领域的应用

背景:氧化石墨烯凭借优越的理化性质和良好的生物相容性能够促进成骨细胞的分化和抑制细菌增殖,有望提高种植体修复的成功率。目的:总结氧化石墨烯在口腔种植修复领域的研究进展。方法:应用计算机检索CNKI、万方、ScienceDirect、PubMed数据库中2000年1月至2024年6月发表的相关文献,检索词为“氧化石墨烯,口腔种植,生物相容性,抗菌机制,成骨细胞,机械性能,化学性能”“graphene oxide,dental Implantation,biocompatibility,antibacterial mechanism,osteoblasts,mechanical properties,chemical properties”。通过阅读文题和摘要进行初步筛选,排除与文章主题不相关的文献,根据纳入和排除标准,最终纳入65篇文献进行综述分析。结果与结论:氧化石墨烯通过自身抗菌及载药抗菌性能可以增加机体先天性免疫保护反应,抑制种植体周围炎的发生和发展。氧化石墨烯可以促进骨髓间充质干细胞的增殖分化,促进成骨细胞、血管内皮细胞的增殖,抑制破骨细胞的增殖,增加种植体与牙槽骨之间骨结合的速率,有利于种植体周围骨的形成和稳定。氧化石墨烯可以促进种植体与龈组织的结合,减少炎症的发生。氧化石墨烯具有低毒性,其生物安全性有待进一步研究。氧化石墨烯涂层赋予了钛种植体表面优良的理化性能,可显著降低种植体折断等并发症的发生,延长种植体使用时间。

Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes

Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association betweenhypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide(approximately 45%-76%) and thiazolidinediones(approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high Hb A1 c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.

Advancements in oral therapeutic drugs for treating SARS-CoV-2 infections:A comprehensive review

SARS-CoV-2 has undergone five major transformations from its original strain,evolving through Alpha,Beta,Gamma,Delta,and now Omicron.The Omicron variant stands out for its high transmissibility,reduced severity,mild symptoms,and low mortality.Today,Omicron infections have become akin to common upper respiratory tract infections,underscoring the critical role of oral therapeutic drugs in clinical settings.These small-molecule oral antivirals are game-changers,effectively preventing mild and moderate cases from escalating to severe conditions and significantly reducing mortality among severe cases.They have emerged as the frontline defenders in the fight against SARS-CoV-2.Currently,eight oral antiviral drugs have been approved for use,including four 3CL protease inhibitors(nirmatrelvir/ritonavir,simnotrelvir/ritonavir,atilotrelvir/ritonavir,ensitrelvir,and leritrelvir),and three RNA polymerase inhibitors(molnupiravir,azvudine,and deuterium remdesivir).These medications are readily available and have ensured an uninterrupted clinical supply.With the establishment of a robust post-infection immune barrier and the widespread clinical use of oral antiviral drugs,the global threat posed by the COVID-19 pandemic has significantly diminished.The relentless march of scientific progress and medical innovation has turned the tide,making COVID-19 a manageable part of our lives.

Treatment of systemic diseases and oral focal infection

Oral lesions are highly correlated with the occurrence and development of many diseases. In addition, the treatment of systemic diseases may aggravate oral focal infections, affect the life quality of patients, interfere with the treatment of systemic diseases, and even cause systemic infection in serious cases. Treatment strategies for systemic diseases may induce or aggravate oral local lesion infections. In specific, administration of oral anti-epileptic drugs and immunosuppressive drugs may induce gingivitis, radiotherapy or chemotherapy for malignant tumors may cause oral mucositis, long-term use of bisphosphonates for inhibition of tumor bone metastasis or prevention of osteoporosis may cause osteonecrosis of the jaw, and allogeneic hematopoietic stem cell transplantation that may cause oral rejection reactions.

A Critical Review on Traditional Herbal Drugs: An Emerging Alternative Drug for Diabetes

Diabetes is a chronic metabolic disease reaching an epidemic proportion in many parts of the world. By the year 2025 it is expected that 333 million people of the world will have diabetes as their main ailment. As today, India assumes the position of the diabetic capital of the world with the highest percentage of its population suffering from diabetes. It is pathetic to mention that in proportion to its people suffering from diabetes, this country has very weak spending power for treatment because of wide spread poverty. Therefore, this review is aimed at opening up new vistas in realizing the therapeutic potential of Ayurveda in treatment of diabetes and other chronic diseases. All drugs which we have discussed in this review have a significant role in therapy of diabetes mellitus.

细胞外囊泡在口腔鳞状细胞癌诊疗中的作用

背景:细胞外囊泡在不同的生理和病理生理条件下由多种细胞类型(包括肿瘤细胞)分泌到细胞外环境中,存在着广泛的生物学信号及细胞之间的信号传导。肿瘤衍生的细胞外囊泡可能会加剧癌症的进展、存活、侵袭和促进血管生成。目的:综述细胞外囊泡在口腔鳞状细胞癌诊疗中的研究进展。方法:由第一作者在Pub Med、万方和中国知网数据库中进行文献检索,关键词为“EVs,Oral squamous cell carcinoma,Diagnosis and treatment,Biopsy,Tissue engineering”及“细胞外囊泡,口腔鳞状细胞癌,诊疗,活检,组织工程”,最终纳入63篇文献进行分析。结果与结论:(1)在口腔鳞状细胞癌唾液活检中,细胞外囊泡作为肿瘤细胞与周围微环境间的信息传递工具,携带包括可溶性蛋白、脂质、DNA和RNA在内的多种生物分子,对口腔鳞状细胞癌的进展起着至关重要的作用,这些微小囊泡不仅在肿瘤的生长和扩散中扮演着关键角色,还提供了有关肿瘤生物学特性的重要信息。(2)唾液活检作为一种非侵入性诊断方法,通过分析其中的细胞外囊泡,可以为口腔鳞状细胞癌的早期诊断和靶向治疗开辟新的可能性。(3)研究发现,细胞外囊泡内含的生物活性分子,如micro RNAs(mi RNAs)和特定蛋白质,能作为口腔鳞状细胞癌的生物标志物,提高早期诊断的准确性。细胞外囊泡中的特定蛋白质如EHD2,CAVIN1,PF4V1和CXCL7等显示了作为新型预测性生物标志物的潜力。(4)此外,文章还强调了细胞外囊泡在口腔鳞状细胞癌治疗中的应用潜力,通过工程化改造,细胞外囊泡可以作为新一代纳米级药物输送系统,增强肿瘤靶向治疗的效率和特异性。(5)未来的研究将进一步深入探索细胞外囊泡在口腔鳞状细胞癌治疗中的作用及其机制,有望改善患者的生存率和生活质量。

创新软件和设备在口服外摆拆零药品智能化管理中的应用

目的通过开发智能创新软件结合独立调配桌对住院药房口服外摆拆零药品进行高效、安全的管理和调配,确保药品的安全供应。方法设置独立外摆药品调配操作台,利用创新软件集成掌上电脑(PDA)智能系统,结合条码扫描导入技术与全自动药品分包机,优化和改进口服外摆药品调剂、加药、有效期维护等易错环节。对比创新软件使用前后口服医嘱平均调剂时长(min),外摆拆零药品月均盘存时长(min)和外摆拆零药品有效期维护平均时长(min)。结果使用创新软件和设备后,口服医嘱平均调剂时长从(218.07±6.72)min缩短至(173.81±6.08)min(P<0.01),均值减少44.26 min;外摆拆零药品月均盘存时长从(156.00±5.29)min缩短至(108.00±2.64)min(P<0.01),均值缩短48.00 min;外摆拆零药品有效期维护平均时长从(147.00±2.64)min缩短至(23.00±3.00)min(P<0.01),均值缩短124 min。结论该项创新应用可解决传统外摆拆零药品容易出现的药品混装、定位混乱、库存数量不明、效期管理困难等问题,实现了药品管理的精细化、科学化,有效提高了药师的工作效率和服务质量,同时也为患者提供了更加安全、便捷的用药服务。

内分泌代谢科门诊糖尿病口服用药的合理性及其与患者降糖达标的相关性

目的分析我院内分泌代谢科门诊糖尿病口服用药的合理性及其与患者降糖达标的相关性,为指导临床合理用药提供指导性建议。方法收集2023年1~12月平顶山市第一人民医院内分泌代谢科门诊56457个口服糖尿病药品处方及24783例患者临床资料,统计分析患者基本情况、口服用药方案、口服药物信息、口服药物用药频度(DDDs)、销售金额、排序比(B/A)及不合理用药情况,并对比合理用药与不合理用药患者糖化血红蛋白(HbA1c)达标情况。结果56457个处方中用药方案频次从高到低依次为含ACEI或ARB方案、合用磺脲类药物方案、含双胍类药物方案及阿司匹林方案;所有口服药物中用药频次前3名的是阿卡波糖片、阿司匹林肠溶片、硝酸异山梨酯片,降糖药物用药频次前3名的是阿卡波糖片、二甲双胍片、卡格列净;在所有处方中,DDDs前5名依次为阿卡波糖片、瑞舒伐他汀钙片、二甲双胍片、氨氯地平片、卡格列净片,B/A前5名依次为瑞舒伐他汀钙片、阿卡波糖片、格列美脲片、氨氯地平片、二甲双胍片;在降糖药物中,DDDs前3名依次为阿卡波糖片、二甲双胍片、卡格列净,B/A前3名依次为阿卡波糖片、格列美脲片、二甲双胍片;56457个处方中不合理处方为813个,占1.44%,用法用量不合理占比最高;24783例患者HbA1c总达标率为93.80%(23247/24783),合理用药患者HbA1c总达标率高于不合理用药患者,差异有统计学意义(P<0.05)。结论该院内分泌代谢科门诊糖尿病口服用药基本合理,患者降糖达标情况良好,但存在少数不合理用药行为,不合理用药会降低降糖达标率,需加强对用药处方的审核。

Pharmacogenomics in oral diseases

The availability of newer technologies for identification and characterization of the human genome has enabled our understanding of the genetic variations in a majority of human diseases.Human genomic sequence varies in less than 1%among the different population group and these differences known as gene polymorphisms are the primary reasons for differences in individuals’response to various drug therapy.Also understanding the genetic changes may enable implementation of targeted therapy,thus providing for effective treatment strategies and minimizing the adverse side effects.Pharmacogenomics is a recent development in the field of personalized medicine which focuses on the genetic determinants of drug response at the levels of entire human genome.It primarily deals with tailoring of drug therapy for every individual based on their genetic make-up and identifying new target in various diseases for drug therapy.While the application of pharmacogenomics in systemic illness is well researched,its role in oral diseases needs documentation.Identifying specific targets in periodontitis,head and neck cancer,infections and genetic disorders can be beneficial in discovery of new drugs.This editorial provides an overview of basics of pharmacoge-nomics,its current role in disease management and its potential role in various head and neck diseases.

Utilization Pattern of Oral Hypoglycemic Agents for Diabetes Mellitus Type 2 Patients Attending Out-Patient Department at a University Hospital in New Delhi

Diabetes mellitus is the chronic disorder emerging as major world health problem which increases the rate of morbidity and mortality. The aim of the present study was to ascertain patterns of prescription of oral hypoglycemic agents to type 2 diabetic patients attending a university hospital, and to assess patient compliance. A prospective, observational and non comparative study was conducted in 200 established diabetes mellitus type 2 patients attending outpatient department at Majeedia Hospital, New Delhi, India. Prescriptions from registered patients were included in the study. Once the consultation by the physician was over, the prescriptions were reviewed and the patients were interviewed. The information was collected in an inhouse designed documentation proforma. In a pool of 200 type 2 diabetics, more than half were female (n=106, 53%). The mean age of the patients were found to be 50.4 ± 11.7 years and mean body mass index, 25.8 ± 4.4 kg/m2. A total of 432 oral hypoglycemic agents were prescribed to the patients. Highly significant number of patients were prescribed combination therapy, (n=143, 71.5%) as compared to monotherapy (n=57, 28.5%),

Oral lichenoid lesion:A review of the literature

The oral lichenoid lesion(OLL) is response that occurs on the oral mucosa. The OLL include allergic responseto the dental materials, drugs, and on graft-vs-host disease(GVHD). OLL to dental material happen when restorative materials, most commonly amalgam, are in direct contact with the mucosa in sensitized individuals. Medications that produce OLL are oral hypoglycemic agents, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory agents. GVHD is a complication in bone marrow transplantation and OLL is a common lesion observed in this disease especially in chronic GVHD. The clinical and histological aspects of OLL are similar to oral lichen planus and turn it difficult to make a differential diagnosis. The purpose of this paper is review about OLL related to the dental materials, drug use and GVHD.