-
Pharmacological Research Jan 2017Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution... (Review)
Review
Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Nanomedicine; Nanoparticles; Neoplasms; Pharmaceutical Preparations; Theranostic Nanomedicine
PubMed: 27865762
DOI: 10.1016/j.phrs.2016.11.014 -
Drug Delivery and Translational Research Mar 2022The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further... (Review)
Review
The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines.
Topics: Drug Delivery Systems; Nanomedicine; Pharmaceutical Preparations; Regenerative Medicine; Research Design
PubMed: 34302274
DOI: 10.1007/s13346-021-01024-2 -
Biological & Pharmaceutical Bulletin 2013In contrast to the general assumption that polyethyleneglycol (PEG)-conjugated substances lack immunogenicity and antigenic, it has been reported that they can elicit... (Review)
Review
In contrast to the general assumption that polyethyleneglycol (PEG)-conjugated substances lack immunogenicity and antigenic, it has been reported that they can elicit antibodies against PEG (mainly anti-PEG immunoglobulin M (IgM)). In patients, the presence of anti-PEG antibodies may limit therapeutic efficacy of PEGylated substances as a consequence of inducing rapid clearance of and neutralizing biological activity of the substances. Here, we introduce specific examples of PEGylated substances including several PEGylated proteins and PEGylated particles (PEGylated nanocarriers) which induce anti-PEG antibody responses. Finally, we emphasize that the immunogenicity of PEGylated substances should be tested in the development stage and that the titer of anti-PEG antibodies in patients should be pre-screened and monitored prior to and throughout a course of treatment with a PEGylated substance.
Topics: Animals; Drug Carriers; Humans; Immunoglobulin M; Nanoparticles; Pharmaceutical Preparations; Polyethylene Glycols; Proteins
PubMed: 23727911
DOI: 10.1248/bpb.b13-00107 -
Sensors (Basel, Switzerland) Feb 2022All pharmaceutical drugs, vaccines, cosmetic products, and many medical breakthroughs must first be approved through clinical research and trials before advancing to... (Review)
Review
All pharmaceutical drugs, vaccines, cosmetic products, and many medical breakthroughs must first be approved through clinical research and trials before advancing to standard practice or entering the marketplace. Clinical trials are sets of tests that are required to determine the safety and efficacy of pharmaceutical compounds, drugs, and treatments. There is one pre-phase and four main clinical phase requirements that every drug must pass to obtain final approval. Analytical techniques play a unique role in clinical trials for measuring the concentrations of pharmaceutical compounds in biological matrices and monitoring the conditions of patients (or volunteers) during various clinical phases. This review focuses on recent analytical methods that are employed to determine the concentrations of drugs and medications in biological matrices, including whole blood, plasma, urine, and breast milk. Four primary analytical techniques (extraction, spectroscopy, chromatography, and electrochemical) are discussed, and their advantages and limitations are assessed. Subsequent to a survey of evidence and results, it is clear that microelectromechanical system (MEMS) based electrochemical sensor and biosensor technologies exhibit several notable advantages over other analytical methods, and their future prospects are discussed.
Topics: Biosensing Techniques; Clinical Trials as Topic; Electrochemical Techniques; Humans; Pharmaceutical Preparations
PubMed: 35214505
DOI: 10.3390/s22041592 -
MedEdPORTAL : the Journal of Teaching... Mar 2021The prevalence of opioid use disorder has increased steadily over the last decade (from 2.2 million in 2010 to 10.2 million in 2018) and with it, a surge in infectious...
INTRODUCTION
The prevalence of opioid use disorder has increased steadily over the last decade (from 2.2 million in 2010 to 10.2 million in 2018) and with it, a surge in infectious complications associated with injection drug use (IDU). Trainees in internal medicine routinely diagnose, manage, and treat patients experiencing these infections in the hospital setting as well as screen for and immunize against other comorbid infections in the ambulatory setting.
METHODS
This 90-minute, case-based, interactive workshop was led by two facilitators, an infectious diseases specialist and a senior internal medicine resident. To evaluate its effectiveness, we used a pre- and postsession survey administered at the beginning and end of the workshop. Learners were asked to rate comfort level in recognizing, managing, and counseling about various IDU-related infections, as well as to answer specific, content-level questions.
RESULT
Thirty of 42 participants who attended the workshop completed the evaluation. There was a statistically significant change in participants' comfort level with diagnosing and managing IDU-associated infections as well as ambulatory standards of care for people who inject drugs (PWID) from pre- to postworkshop.
DISCUSSION
Our workshop focused on the management and prevention of infections among PWID in both the inpatient and ambulatory settings. Learners demonstrated increased comfort in managing these conditions.
Topics: Hospitals; Humans; Infections; Inpatients; Pharmaceutical Preparations; Prevalence; Substance Abuse, Intravenous
PubMed: 33816787
DOI: 10.15766/mep_2374-8265.11124 -
Breast Cancer Research : BCR May 2023Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship... (Review)
Review
Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.
Topics: Female; Humans; Progesterone; Breast Neoplasms; Menstrual Cycle; Estrogens; Estradiol; Pharmaceutical Preparations
PubMed: 37254150
DOI: 10.1186/s13058-023-01661-0 -
Advanced Drug Delivery Reviews Jun 2014The complex process of oral drug absorption is influenced by a host of drug and formulation properties as well as their interaction with the gastrointestinal environment... (Review)
Review
The complex process of oral drug absorption is influenced by a host of drug and formulation properties as well as their interaction with the gastrointestinal environment in terms of drug solubility, dissolution, permeability and pre-systemic metabolism. For adult dosage forms the use of biopharmaceutical tools to aid in the design and development of medicinal products is well documented. This review considers current literature evidence to guide development of bespoke paediatric biopharmaceutics tools and reviews current understanding surrounding extrapolation of adult methodology into a paediatric population. Clinical testing and the use of in silico models were also reviewed. The results demonstrate that further work is required to adequately characterise the paediatric gastrointestinal tract to ensure that biopharmaceutics tools are appropriate to predict performance within this population. The most vulnerable group was found to be neonates and infants up to 6 months where differences from adults were greatest.
Topics: Administration, Oral; Animals; Biopharmaceutics; Chemistry, Pharmaceutical; Child; Humans; Intestinal Absorption; Legislation, Drug; Models, Biological; Pediatrics; Permeability; Pharmaceutical Preparations; Solubility
PubMed: 24189013
DOI: 10.1016/j.addr.2013.10.006 -
European Cells & Materials Mar 2021The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic... (Review)
Review
The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.
Topics: Animals; Bone and Bones; Humans; Periodontitis; Pharmaceutical Preparations
PubMed: 33733451
DOI: 10.22203/eCM.v041a20 -
Journal of Evidence-based Integrative... 2022Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The... (Review)
Review
Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs.This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors.Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included.Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB.Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.
Topics: Biological Products; Cardiovascular Diseases; Endothelium; Heart Disease Risk Factors; Humans; Hypertension; Pharmaceutical Preparations; Risk Factors
PubMed: 35849068
DOI: 10.1177/2515690X221113327 -
British Journal of Clinical Pharmacology Oct 2020Even the most effective drug product may be used improperly and thus ultimately prove ineffective if it does not meet the perceptual, motor and cognitive capacities of... (Review)
Review
Even the most effective drug product may be used improperly and thus ultimately prove ineffective if it does not meet the perceptual, motor and cognitive capacities of its target users. Currently, no comprehensive guideline for systematically designing user-centric drug products that would help prevent such limitations exists. We have compiled a list of approximate but nonetheless useful strategies-heuristics-for implementing a user-centric design of drug products and drug product portfolios. First, we present a general heuristic for user-centric design based on the framework of Human Factors and Ergonomics (HF/E). Then we demonstrate how to implement this general heuristic for older drug users (i.e., patients and caregivers aged 65 years and older) and with respect to three specific challenges (use-cases) of medication management: (A) knowing what drug product to take/administer, (B) knowing how and when to take/administer it, and (C) actually taking/administering it. The presented heuristics can be applied prospectively to include existing knowledge about user-centric design at every step during drug discovery, pharmaceutical drug development, and pre-clinical and clinical trials. After a product has been released to the market, the heuristics may guide a retrospective analysis of medication errors and barriers to product usage as a basis for iteratively optimizing both the drug product and its portfolio over their life cycle.
Topics: Drug Development; Ergonomics; Heuristics; Humans; Pharmaceutical Preparations; Retrospective Studies
PubMed: 31663157
DOI: 10.1111/bcp.14134