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Current Gastroenterology Reports Nov 2020The aim of this review is to evaluate emerging, novel therapies for the prevention of post-ERCP pancreatitis. (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to evaluate emerging, novel therapies for the prevention of post-ERCP pancreatitis.
RECENT FINDINGS
Rectal indomethacin reduces the risk of pancreatitis in low- and average-risk patients, who comprise the majority of patients undergoing ERCP. An 8-h protocol of aggressive lactated Ringer's reduces the risk of pancreatitis in average-risk patients. Sublingual nitrate may provide additional benefit to rectal NSAIDs in preventing PEP. A tacrolimus trough > 2.5 ng/mL was recently shown to be associated with a lower risk of PEP in liver transplant patients undergoing ERCP. Routine usage of rectal indomethacin in all patients undergoing ERCP reduces the risk of PEP. Pancreatic-duct stents reduce the risk of PEP in high-risk patients. There is emerging data that aggressive hydration with lactated Ringer's and nitrates may further reduce PEP. Tacrolimus is a promising potential agent to prevent PEP but needs further clinical study.
Topics: Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Humans; Immunosuppressive Agents; Indomethacin; Nitro Compounds; Pancreatic Ducts; Pancreatitis; Ringer's Lactate; Stents; Tacrolimus
PubMed: 33188441
DOI: 10.1007/s11894-020-00796-w -
International Journal of Biological... Apr 2022The design of carriers for insulin delivery has recently attracted major research attentions in the biomedical field. In general, the release of drug from polymers is... (Review)
Review
The design of carriers for insulin delivery has recently attracted major research attentions in the biomedical field. In general, the release of drug from polymers is driven via a variety of polymers. Several mechanisms such as matrix release, leaching of drug, swelling, and diffusion are usually adopted for the release of drug through polymers. Insulin is one of the most predominant therapeutic drugs for the treatment of both diabetes mellitus; type-I (insulin-dependent) and type II (insulin-independent). Currently, insulin is administered subcutaneously, which makes the patient feel discomfort, pain, hyperinsulinemia, allergic responses, lipodystrophy surrounding the injection area, and occurrence of miscarried glycemic control. Therefore, significant research interest has been focused on designing and developing new insulin delivery technologies to control blood glucose levels and time, which can enhance the patient compliance simultaneously through alternative routes as non-invasive insulin delivery. The aim of this review is to emphasize various non-invasive insulin delivery mechanisms including oral, transdermal, rectal, vaginal, ocular, and nasal. In addition, this review highlights different smart stimuli-responsive insulin delivery systems including glucose, pH, enzymes, near-infrared, ultrasound, magnetic and electric fields, and the application of various polymers as insulin carriers. Finally, the advantages, limitations, and the effect of each non-invasive route on insulin delivery are discussed in detail.
Topics: Administration, Cutaneous; Diabetes Mellitus; Drug Delivery Systems; Humans; Insulin; Polymers
PubMed: 35101478
DOI: 10.1016/j.ijbiomac.2022.01.134 -
Frontiers in Pharmacology 2019Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or... (Review)
Review
Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local and systemic actions. The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect. Therefore, rectal drug delivery can provide significant local and systemic levels for various drugs, despite the relatively small surface area of the rectal mucosa. Further development and optimization of rectal drug formulations have led to improvements in drug bioavailability, formulation retention, and drug release kinetics. However, despite the pharmaceutical advances in rectal drug delivery, very few of them have translated to the clinical phase. This review will address the physiological and pharmaceutical considerations influencing rectal drug delivery as well as the conventional and novel drug delivery approaches. The translational challenges and development aspects of novel formulations will also be discussed.
PubMed: 31680970
DOI: 10.3389/fphar.2019.01196 -
Current Opinion in Endocrinology,... Oct 2020The aim of the article is to present the basics of oral levothyroxine (LT4) absorption, reasons why patients may have persistently elevated serum thyroid stimulation... (Review)
Review
PURPOSE OF REVIEW
The aim of the article is to present the basics of oral levothyroxine (LT4) absorption, reasons why patients may have persistently elevated serum thyroid stimulation hormone (TSH) levels, and alternative strategies for LT4 dosing.
RECENT FINDINGS
Although oral LT4 tablets are most commonly used for thyroid hormone replacement in patients with hypothyroidism, case studies report that liquid oral LT4, intravenous, intramuscular, and rectal administration of LT4 can successfully treat refractory hypothyroidism.
SUMMARY
Hypothyroidism is one of the most common endocrine disorders encountered by primary care physicians and endocrinologists. LT4 is one of the most widely prescribed medications in the world and it is the standard of care treatment for hypothyroidism. Generally, hypothyroid patients will be treated with LT4 tablets to be taken orally, and monitoring will occur with routine serum thyroid tests, including TSH concentrations. However, many patients fail to maintain serum TSH levels in the target range while managed on oral LT4 tablets. A subset of these patients would be considered to have poorly controlled hypothyroidism, sometimes termed refractory hypothyroidism. For these patients, optimization of ingestion routines and alternative formulations and routes of administration of LT4 can be considered, including oral liquid, intravenous, intramuscular, and even rectal formulations.
Topics: Administration, Oral; Dosage Forms; Drug Administration Routes; Drug Compounding; Gels; Humans; Hypothyroidism; Tablets; Thyrotropin; Thyroxine
PubMed: 32740045
DOI: 10.1097/MED.0000000000000558 -
Clinical Drug Investigation Jun 2023Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects.
METHODS
An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study.
RESULTS
All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration (T) of 1.00 h, and mean values of the peak concentration (C) and area under the concentration-time curve (AUC) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam.
CONCLUSION
Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study.
CLINICAL TRIAL REGISTRATION
The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).
Topics: Child; Female; Humans; Male; Administration, Oral; Administration, Rectal; Area Under Curve; Cross-Over Studies; East Asian People; Healthy Volunteers; Hypnotics and Sedatives; Midazolam; Administration, Intravenous; Gels; Biological Availability
PubMed: 37270744
DOI: 10.1007/s40261-023-01276-5 -
Current Opinion in Urology May 2023Prostate biopsy is commonly performed in men suspected to have prostate cancer. It has traditionally been performed using a transrectal approach, but transperineal... (Review)
Review
PURPOSE OF REVIEW
Prostate biopsy is commonly performed in men suspected to have prostate cancer. It has traditionally been performed using a transrectal approach, but transperineal prostate biopsy has been increasingly adopted in part because of its lower associated infectious risk. We review recent studies evaluating the rate of potentially life-threatening post-biopsy sepsis and potential preventive strategies.
RECENT FINDINGS
After performing a comprehensive literature search, 926 records were screened and 17 studies published in 2021 or 2022 were found to be relevant. Studies varied in periprocedural perineal and transrectal preparation, antibiotic prophylaxis, and definition of sepsis. The sepsis rates after transperineal ultrasound-guided versus transrectal ultrasound-guided biopsy ranged between 0 and 1 versus 0.4 and 9.8%. Mixed efficacy was found for the topical application of antiseptics before transrectal biopsy to decrease postprocedural sepsis. Promising strategies include the use of topical rectal antiseptics before transrectal prostate biopsy and using a rectal swab to guide the antibiotic selection and the route of the biopsy.
SUMMARY
The transperineal approach to biopsy is increasingly used because of lower associated sepsis rates. Our review of the recent literature supports this practice pattern change. Hence, transperineal biopsy should be offered as an option to all men.
Topics: Male; Humans; Prostate; Biopsy; Rectum; Prostatic Neoplasms; Image-Guided Biopsy; Sepsis; Anti-Infective Agents, Local
PubMed: 36861767
DOI: 10.1097/MOU.0000000000001083 -
International Journal of Pharmaceutics Feb 2023Diabetes mellitus is a metabolic endocrine disease characterized by chronic hyperglycemia with disturbances in metabolic processes, such as those related to... (Review)
Review
Diabetes mellitus is a metabolic endocrine disease characterized by chronic hyperglycemia with disturbances in metabolic processes, such as those related to carbohydrates, fat, and protein. There are two main types of this disease: type 1 diabetes (T1D) and type 2 diabetes (T2D). Insulin therapy is pivotal to the management of diabetes. Over the last two decades, many routes of administration, including nasal, pulmonary, rectal, transdermal, buccal, and ocular, have been investigated. Nevertheless, subcutaneous parenteral administration is still the most common route for insulin therapy. To overcome poor bioavailability and the barriers to oral insulin absorption, novel approaches in the field of oral drug delivery and administration have been brought about by the coalescence of different branches of nanoscience and nanotechnology, such as nanomedicine, nano-biochemistry, and nano-pharmacy. Novel drug delivery systems, including nanoparticles, nano-platforms, and nanocarriers, have been suggested. The objective of this review is to provide an update on the various promising approaches that have been explored and evaluated for the safe and efficient oral and buccal administration of insulin.
Topics: Humans; Insulin; Diabetes Mellitus, Type 2; Drug Delivery Systems; Diabetes Mellitus, Type 1; Administration, Cutaneous; Administration, Oral; Nanoparticles
PubMed: 36681204
DOI: 10.1016/j.ijpharm.2023.122623 -
ACS Applied Materials & Interfaces Jun 2022An active flavonoid compound rutin was incorporated into a guanosine phenylborate hydrogel () by a stimuli-responsive borate ester linkage for the treatment of...
An active flavonoid compound rutin was incorporated into a guanosine phenylborate hydrogel () by a stimuli-responsive borate ester linkage for the treatment of inflammatory bowel disease (IBD). The components and morphology of the drug delivery system were characterized by NMR, UV-vis spectroscopy, and AFM. Rheological measurements revealed the required injectability and self-healing ability, which contributed to its application in rectal administration. The cell assays proved the excellent compatibility and safety of the system, and a possible pathway to form multicellular aggregates. drug-release studies showed that the hydrogel exhibited good stability in physiological medium, and the drug was almost completely released (more than 90 wt % after 24 h of incubation) in acidic pH and excessive ROS-containing medium, realizing the dual-responsive release of pH/ROS. activities of the hydrogel showed higher therapeutic efficacy than free rutin in a colitis mice model, and it could significantly inhibit overexpressed inflammatory cytokines, including TNF-α and IL-6. Degradation studies of the hydrogel provided further evidence for the safety of its application. The work provided a simple strategy to prepare a G-quadruplex drug carrier, which was expected to achieve multi-drug delivery.
PubMed: 35642748
DOI: 10.1021/acsami.2c02295 -
International Journal of Biological... May 2022Despite tremendous efforts, the world continues its fight against the common chronic disease-diabetes. Diabetes is caused by elevated glucose levels in the blood, which... (Review)
Review
Despite tremendous efforts, the world continues its fight against the common chronic disease-diabetes. Diabetes is caused by elevated glucose levels in the blood, which can lead to several complications like glaucoma, cataract, kidney failure, diabetic ketoacidosis, heart attack, and stroke. According to recent statistics, China, India, and the US rank at the top three positions with regards to the number of patients affected by diabetes. Ever since its discovery, insulin is one of the major therapeutic molecules that is used to control the disease in the diabetic population, worldwide. The most common route of insulin administration has been the subcutaneous route. However, the limitations associated with this route have motivated global efforts to explore alternative strategies to deliver insulin, including pulmonary, transdermal, nasal, rectal, buccal, and oral routes. Oral insulin delivery is the most convenient and patient-centered route. However, the oral route is also associated with numerous drawbacks that present significant challenges to the scientific fraternity. The human physiological system acts as a formidable barrier to insulin, limiting its bioavailability. The present review covers the major barriers against oral insulin delivery and explains formulation strategies that have been adopted to overcome these barriers. The review focuses on oral insulin delivery strategies (OIDS) for increasing the bioavailability of oral insulin, including nanoparticles, microparticles, nano-in-microparticles, hydrogels, tablets, capsules, intestinal patches, and use of ionic liquids. It also highlights some of the notable recent advancements and clinical trials in oral insulin delivery. This formulation based OIDS may significantly improve patient compliance in the treatment of diabetes.
Topics: Administration, Oral; Diabetes Mellitus; Drug Delivery Systems; Humans; Hypoglycemic Agents; Insulin; Nanoparticles
PubMed: 35346680
DOI: 10.1016/j.ijbiomac.2022.03.144 -
Clinical Imaging Dec 2021Ingestion, inhalation, and insertion of foreign bodies (FB) are commonly encountered problems in the emergency departments (ED). Radiologists pay a key role in their... (Review)
Review
INTRODUCTION
Ingestion, inhalation, and insertion of foreign bodies (FB) are commonly encountered problems in the emergency departments (ED). Radiologists pay a key role in their diagnosis and management. Selecting an appropriate imaging modality is important depending on the route of entry and reported type of FB. Diagnosing FB is time sensitive and requires radiologists to be astute and familiar with varied imaging appearances of FB. In this article, we review imaging features of most common FB seen in clinical practice and their complications.
TEACHING POINTS
SUMMARY: FB in body orifices are frequently seen in the ED. Imaging plays a pivotal role in the management in majority of the cases. In this article, we present several cases of commonly encountered FB.
Topics: Diagnostic Imaging; Emergency Service, Hospital; Foreign Bodies; Humans; Radiologists
PubMed: 34333353
DOI: 10.1016/j.clinimag.2021.07.006