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Advanced Drug Delivery Reviews 2020Considering the multifaceted protective and homeostatic roles of the complement system, many consequences arise when drug carriers, and particulate pharmaceutical... (Review)
Review
Considering the multifaceted protective and homeostatic roles of the complement system, many consequences arise when drug carriers, and particulate pharmaceutical formulations clash with complement proteins, and trigger complement cascade. Complement activation may induce formulation destabilization, promote opsonization, and affect biological and therapeutic performance of pharmaceutical nano- and micro-particles. In some cases, complement activation is beneficial, where complement may play a role in prophylactic protection, whereas uncontrolled complement activation is deleterious, and contributes to disease progression. Accordingly, design initiatives with particulate medicines should consider complement activation properties of the end formulation within the context of administration route, dosing, systems biology, and therapeutic perspective. Here we examine current progress in mechanistic processes underlying complement activation by pre-clinical and clinical particles, identify opportunities and challenges ahead, and suggest future directions in nanomedicine-complement interface research.
Topics: Animals; Complement Activation; Complement System Proteins; Drug Carriers; Humans; Microspheres; Nanoparticles; Pharmaceutical Preparations
PubMed: 32389761
DOI: 10.1016/j.addr.2020.04.012 -
International Journal of Pharmaceutics Jan 2023Three-dimensional (3D) printing is an emerging technology with great potential in pharmaceutical applications, providing innovative solutions for both patients and... (Review)
Review
Three-dimensional (3D) printing is an emerging technology with great potential in pharmaceutical applications, providing innovative solutions for both patients and pharmaceutical industry. This technology offers precise construction of the structure of dosage forms and can benefit drug product design by providing versatile release modes to meet clinical needs and facilitating patient-centric treatment, such as personalized dosing, accommodate treatment of specific disease states or patient populations. Utilization of 3D printing also facilitates digital drug product development and manufacturing. Development of 3D printing at early clinical stages and commercial scale pharmaceutical manufacturing has substantially advanced in recent years. In this review, we discuss how 3D printing accelerates early-stage drug development, including pre-clinical research and early phase human studies, and facilitates late-stage product manufacturing as well as how the technology can benefit patients. The advantages, current status, and challenges of employing 3D printing in large scale manufacturing and personalized dosing are introduced respectively. The considerations and efforts of regulatory agencies to address 3D printing technology are also discussed.
Topics: Humans; Technology, Pharmaceutical; Drug Industry; Drug Delivery Systems; Printing, Three-Dimensional; Pharmaceutical Preparations
PubMed: 36509225
DOI: 10.1016/j.ijpharm.2022.122480 -
Biomedicine & Pharmacotherapy =... Sep 2021Repositioning or "repurposing" of existing therapies for indications of alternative disease is an attractive approach that can generate lower costs and require a shorter... (Review)
Review
Repositioning or "repurposing" of existing therapies for indications of alternative disease is an attractive approach that can generate lower costs and require a shorter approval time than developing a de novo drug. The development of experimental drugs is time-consuming, expensive, and limited to a fairly small number of targets. The incorporation of separate and complementary data should be used, as each type of data set exposes a specific feature of organism knowledge Drug repurposing opportunities are often focused on sporadic findings or on time-consuming pre-clinical drug tests which are often not guided by hypothesis. In comparison, repurposing in-silico drugs is a new, hypothesis-driven method that takes advantage of big-data use. Nonetheless, the widespread use of omics technology, enhanced data storage, data sense, machine learning algorithms, and computational modeling all give unparalleled knowledge of the methods of action of biological processes and drugs, providing wide availability, for both disease-related data and drug-related data. This review has taken an in-depth look at the current state, possibilities, and limitations of further progress in the field of drug repositioning.
Topics: Animals; Big Data; Computer Simulation; Drug Delivery Systems; Drug Discovery; Drug Repositioning; Humans; Machine Learning; Pharmaceutical Preparations
PubMed: 34153846
DOI: 10.1016/j.biopha.2021.111638 -
Advanced Drug Delivery Reviews Nov 2023Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical... (Review)
Review
Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.
Topics: Animals; Humans; Excipients; Drug Compounding; Pharmaceutical Preparations; Intestines; Surface-Active Agents
PubMed: 37739041
DOI: 10.1016/j.addr.2023.115086 -
BMC Geriatrics Jul 2009Older people are commonly prescribed complex multi-drug regimens while also experiencing declines in the cognitive and physical abilities required for medication... (Review)
Review
BACKGROUND
Older people are commonly prescribed complex multi-drug regimens while also experiencing declines in the cognitive and physical abilities required for medication management, leading to increased risk of medication errors and need for assisted living. The purpose of this study was to review published instruments designed to assess patients' capacity to self-administer medications.
METHODS
Searches of Medline, EMBASE, CINAHL, PsycINFO, International Pharmaceutical Abstracts, Health and Psychosocial Instruments, Google, and reference lists of identified publications were conducted to identify English-language articles describing development and validation of instruments designed to assess patients' capacity to self-administer medications. Methodological quality of validation studies was rated independently against published criteria by two reviewers and reliability and validity data were reviewed.
RESULTS
Thirty-two instruments were identified, of which 14 met pre-defined inclusion criteria. Instruments fell into two categories: those that used patients' own medications as the basis for assessment and those that used a simulated medication regimen. The quality of validation studies was generally low to moderate and few instruments were subjected to reliability testing. Most instruments had some evidence of construct validity, through associations with tests of cognitive function, health literacy, activities of daily living or measures of medication management or adherence. Only one instrument had sensitivity and specificity data with respect to prediction of medication-related outcomes such as adherence to therapy. Only three instruments had validity data from more than one independent research group.
CONCLUSION
A number of performance-based instruments exist to assess patients' capacity to manage their own medications. These may be useful for identifying physical and cognitive barriers to successful medication management, but further studies are needed to determine whether they are able to accurately and reliably predict medication outcomes.
Topics: Humans; Medication Errors; Patient Compliance; Pharmaceutical Preparations; Prescription Drugs; Self Care; Validation Studies as Topic
PubMed: 19594913
DOI: 10.1186/1471-2318-9-27 -
Molecules (Basel, Switzerland) Jan 2023Central nervous system (CNS) disorders are a therapeutic area in drug discovery where demand for new treatments greatly exceeds approved treatment options. This is... (Review)
Review
Central nervous system (CNS) disorders are a therapeutic area in drug discovery where demand for new treatments greatly exceeds approved treatment options. This is complicated by the high failure rate in late-stage clinical trials, resulting in exorbitant costs associated with bringing new CNS drugs to market. Computer-aided drug design (CADD) techniques minimise the time and cost burdens associated with drug research and development by ensuring an advantageous starting point for pre-clinical and clinical assessments. The key elements of CADD are divided into ligand-based and structure-based methods. Ligand-based methods encompass techniques including pharmacophore modelling and quantitative structure activity relationships (QSARs), which use the relationship between biological activity and chemical structure to ascertain suitable lead molecules. In contrast, structure-based methods use information about the binding site architecture from an established protein structure to select suitable molecules for further investigation. In recent years, deep learning techniques have been applied in drug design and present an exciting addition to CADD workflows. Despite the difficulties associated with CNS drug discovery, advances towards new pharmaceutical treatments continue to be made, and CADD has supported these findings. This review explores various CADD techniques and discusses applications in CNS drug discovery from 2018 to November 2022.
Topics: Computer-Aided Design; Ligands; Drug Design; Psychotropic Drugs; Pharmaceutical Preparations
PubMed: 36770990
DOI: 10.3390/molecules28031324 -
Alimentary Pharmacology & Therapeutics Sep 2014Obesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically... (Review)
Review
BACKGROUND
Obesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically undisputed, but a growing data pool from long-term follow-up reveals increasing evidence of potentially severe nutritional and pharmacological consequences.
AIMS
To assess the prevalence, causes and symptoms of complications after obesity surgery, to elucidate and compare therapy recommendations for macro- and micronutrient deficiencies, and to explore surgically-induced effects on drug absorption and bioavailability, discussing ramifications for long-term therapy and prophylaxis.
METHODS
PubMed, Embase and MEDLINE were searched using terms including, but not limited to, bariatric surgery, gastric bypass, obesity surgery and Roux-en-Y, coupled with secondary search terms, e.g. anaemia, micronutrients, vitamin deficiency, bacterial overgrowth, drug absorption, pharmacokinetics, undernutrition. All studies in English, French or German published January 1980 through March 2014 were included.
RESULTS
Macro- and micronutrient deficiencies are common after obesity surgery. The most critical, depending on surgical technique, are hypoalbuminemia (3-18%) and deficiencies of vitamins B1 (≤49%), B12 (19-35%) and D (25-73%), iron (17-45%) and zinc (12-91%). Many drugs commonly administered to obese patients (e.g. anti-depressants, anti-microbials, metformin) are subject to post-operative and/or PPI-associated changes affecting bioavailability and absorption.
CONCLUSIONS
Complications are associated with pre-operative and/or post-operative malnutrition or procedure-related changes in intake, absorption and drug bioavailability. The high prevalence of nutrient deficiencies after obesity surgery makes life-long nutritional monitoring and supplementation essential. Post-operative changes to drug absorption and bioavailability in bariatric patients cast doubt on the validity of standard drug dosage and administration recommendations.
Topics: Bariatric Surgery; Biological Availability; Deficiency Diseases; Humans; Hypoalbuminemia; Obesity, Morbid; Pharmaceutical Preparations; Pharmacokinetics; Postoperative Complications
PubMed: 25078533
DOI: 10.1111/apt.12872 -
AIMS Public Health 2021Geriatrics as an educational topic has been a high priority in current health care. The innovative Age-Friendly health system with the 4Ms structure (what Matters most,...
BACKGROUND
Geriatrics as an educational topic has been a high priority in current health care. The innovative Age-Friendly health system with the 4Ms structure (what Matters most, Medication, Mentation, Mobility) needs to be integrated into oral health and dental services training. The purpose of this study is to respond to one question: are the graduating general dentists trained and prepared to treat medically vulnerable elderly in communities?
METHODS
All pre-doctorate dental students from first year to fourth year were invited to voluntarily respond to an online survey provided on Qualtrics. The survey provided examples of two broken molar teeth that need extraction. First, students were asked how comfortable they felt extracting the two molars based on the x-rays. Then, the question was repeated to evaluate if they felt comfortable with extracting the teeth in a patient with one chronic condition and related medication(s). Finally, the students were again questioned whether they feel comfortable to provide the same service to medically vulnerable patients with multiple health conditions and polypharmacy.
RESULTS
The majority of students who participated in this study said they were comfortable with extracting the teeth of patients without any chronic condition. However, many more chose to refer medically vulnerable patients with multiple chronic conditions and polypharmacy to a specialist.
CONCLUSIONS
Dental education in many U.S. dental schools may provide adequate education and create competent general dentists. Yet, the competency and confidence required for dentists to be able to treat older adults with multiple health conditions and using prescribed or over-the-counter medication is insufficient.
PubMed: 34786428
DOI: 10.3934/publichealth.2021054 -
International Journal of Nanomedicine 2021Pancreatic cancer is one of the most malignant tumors with one of the worst survival rates due to its insidious onset and resistance to therapies. Most therapeutics show... (Review)
Review
Pancreatic cancer is one of the most malignant tumors with one of the worst survival rates due to its insidious onset and resistance to therapies. Most therapeutics show a desired anticancer effect in vitro; however, very poor efficacy in vivo because of the limited drug delivery and penetration into pancreatic tumors attributed to the abundance of the tumor stroma, ie, the fibrotic tumor microenvironment surrounding the cancer cells. For a better understanding of the challenges posed by the pancreatic tumor stroma, we outline the key features of the tumor microenvironment. Then we highlight major strategies used to tackle the challenges to improve drug penetration into the tumor and achieve enhanced efficacy (pre)clinically. Furthermore, we describe nanomedicine strategies to modulate the tumor stroma, degrade the extracellular matrix, and co-deliver multi-functional drugs, to improve the chemotherapeutics delivery and penetration into pancreatic tumors.
Topics: Carcinoma, Pancreatic Ductal; Drug Delivery Systems; Humans; Nanomedicine; Pancreatic Neoplasms; Pharmaceutical Preparations; Tumor Microenvironment
PubMed: 34552327
DOI: 10.2147/IJN.S279192 -
AAPS PharmSciTech Mar 2021Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal... (Review)
Review
Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.
Topics: Drug Delivery Systems; Drug Packaging; Humans; Intravitreal Injections; Needles; Pharmaceutical Preparations; Sterilization; Syringes
PubMed: 33709236
DOI: 10.1208/s12249-021-01949-4