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International Journal of Pharmaceutics Sep 2020How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic... (Review)
Review
How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic peptide products and the formulations approved by the United States Food and Drug administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). This review also provides an in-depth analysis of dosage forms and administration routes for delivering peptide therapeutics, including injectables, oral dosage forms, and other routes of administration. We discuss the function of excipients in parenteral formulations in detail, since most peptide therapeutics are parenterally administered. We provide case studies of alternate delivery routes and dosage forms. Based on our analysis, therapeutic peptides administered as injectables remain the most commonly used dosage forms, particularly in the form of subcutaneous, intravenous, or intramuscular injections. In addition, therapeutic peptides are formulated to achieve prolonged release, often through the use of polymer carriers. The limited number of oral therapeutic peptide products and their poor absorption and subsequent low bioavailability indicate a need for new technologies to broaden the formulation design space. Therapeutic peptide products may also be delivered through other administration routes, including intranasal, implant, and sublingual routes. Therefore, an in-depth understanding of how therapeutic peptides are now formulated and administered is essential to improve peptide delivery, improve patient compliance, and reduce the healthcare burden for these crucial therapeutic agents.
Topics: Administration, Intranasal; Administration, Oral; Drug Delivery Systems; Excipients; Humans; Peptides; United States
PubMed: 32622810
DOI: 10.1016/j.ijpharm.2020.119491 -
Toxics Aug 2022Echinocandins selectively inhibit fungal cell wall synthesis and, therefore, have few side effects. However, there are reports of hemodynamic and cardiac complications....
Echinocandins selectively inhibit fungal cell wall synthesis and, therefore, have few side effects. However, there are reports of hemodynamic and cardiac complications. We conducted this study to investigate the effects of caspofungin both on the noninvasive echocardiographic indices of myocardial function and myocardial injury based on serum high-sensitivity cardiac troponin I (hs-cTnI) levels. This study was conducted on patients treated for candidemia. The hs-cTnI level and echocardiographic parameters were measured before and 1 h after the infusion of the induction dose of caspofungin. Data were compared between central and peripheral venous drug administration routes. Fifteen patients were enrolled in the study. There were no significant differences in the echocardiographic parameters between the baseline and post-treatment period. The mean hs-cTnI level exhibited a significant rise following drug administration (0.24 ± 0.2 ng/mL vs 0.32 ± 0.3 ng/mL; = 0.006). There was also a significant difference concerning the hs-cTnI level between central and peripheral venous drug administration routes ( = 0.034). Due to differences in the hs-cTnI level, it appears that the administration of caspofungin may be associated with myocardial injury. Our findings also showed a higher possibility of cardiotoxicity via the central venous administration route.
PubMed: 36136486
DOI: 10.3390/toxics10090521 -
Pharmacological Reports : PR Apr 2023Clinical management of COVID-19 has been a daunting task. Due to the lack of specific treatment, vaccines have been regarded as the first line of defence. Innate... (Review)
Review
Clinical management of COVID-19 has been a daunting task. Due to the lack of specific treatment, vaccines have been regarded as the first line of defence. Innate responses and cell-mediated systemic immunity, including serum antibodies, have been the primary focus of practically all studies of the immune response to COVID-19. However, owing to the difficulties encountered by the conventional route, alternative routes for prophylaxis and therapy became the need of the hour. The first site invaded by SARS-CoV-2 is the upper respiratory tract. Nasal vaccines are already in different stages of development. Apart from prophylactic purposes, mucosal immunity can be exploited for therapeutic purposes too. The nasal route for drug delivery offers many advantages over the conventional route. Besides offering a needle-free delivery, they can be self-administered. They present less logistical burden as there is no need for refrigeration. The present article focuses on various aspects of nasal spray for eliminating COVID-19.
Topics: Humans; COVID-19; Nasal Sprays; SARS-CoV-2; Administration, Intranasal; Vaccines
PubMed: 36848033
DOI: 10.1007/s43440-023-00463-7 -
Frontiers in Bioengineering and... 2020For the past 50 years, the route of inhalation has been utilized to administer therapies to treat a variety of respiratory and pulmonary diseases. When compared with... (Review)
Review
For the past 50 years, the route of inhalation has been utilized to administer therapies to treat a variety of respiratory and pulmonary diseases. When compared with other drug administration routes, inhalation offers a targeted, non-invasive approach to deliver rapid onset of drug action to the lung, minimizing systemic drug exposure and subsequent side effects. However, despite advances in inhaled therapies, there is still a need to improve the preclinical screening and the efficacy of inhaled therapeutics. Innovative models of respiratory physiology to determine therapeutic efficacy of inhaled compounds have included the use of organoids, micro-engineered lung-on-chip systems and sophisticated bench-top platforms to enable a better understanding of pulmonary mechanisms at the molecular level, rapidly progressing inhaled therapeutic candidates to the clinic. Furthermore, the integration of complementary models, such as precision-cut lung slices (PCLS) and isolated perfused lung platforms have further advanced preclinical drug screening approaches by providing relevance. In this review, we address the challenges and advances of models and discuss the implementation of inhaled drug screening models. Specifically, we address the importance of understanding human pulmonary mechanisms in assessing strategies of the preclinical screening of drug efficacy, toxicity and delivery of inhaled therapeutics.
PubMed: 33195144
DOI: 10.3389/fbioe.2020.581995 -
Pharmaceutical Medicine Nov 2023Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This... (Review)
Review
Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This is as close to the tissue of interest that we can get, although biopsies may be obtained to give "tissue levels" of drugs. Ultimately, the goal of PK is to understand how long the drug is actually engaged with the target in the tissue of interest after a dose has been administered. Most drugs at some point in their development will have been administered intravenously (IV), which acts as the standard for 100% bioavailability. By comparing various routes of administration to IV, the percentage of drug delivered to the plasma, on a dose-normalized basis, can be calculated and is referred to as the "absolute bioavailability". As pharmacology has advanced and more drugs have become available, many older products have been reformulated to be given by routes other than those originally intended (often oral). As the drawbacks of oral (or IV) administration have become better appreciated, non-oral, non-IV formulations and methods of administration have become more popular. Nasal administration is one route that has historically been overlooked as an alternative to oral administration-particularly for products needing rapid and non-invasive access to the target tissue-mostly via the blood stream. But attention is now focused on nasal administration for direct access to the brain, as that has the potential to bypass the blood-brain-barrier (BBB), which not even IV administration can always achieve. Assessing PK for these drugs targeting the brain may require serial sampling of the cerebrospinal fluid (CSF), making PK assessments of CNS drugs more invasive and complex, but still possible in future product development. However, we are now seeing more drugs reformulated for nasal delivery to gain faster systemic levels than oral administration (especially in patients with known or suspected gastrointestinal dysmotility), while avoiding the use of needles. For example, in recent years several different formulations and delivery methods for an old drug, dihydroergotamine (DHE), have been developed and these show very different characteristics, suggesting that delivery to different parts of the nose may have very different PK profiles. This review summarizes the systemic PK of different nasal DHE options that have been, or are being, developed and suggests that delivery of drugs to the upper nasal space (UNS) may represent an optimal target. Further research is required to ascertain if this route could also be utilized for direct administration to the CNS (as an attractive alternative to intrathecal delivery) via the olfactory or trigeminal nerves-but already preclinical data (and some human data) suggest this is entirely possible.
Topics: Humans; Pharmaceutical Preparations; Administration, Intranasal; Brain; Blood-Brain Barrier; Central Nervous System Agents
PubMed: 37537422
DOI: 10.1007/s40290-023-00495-7 -
European Review For Medical and... Dec 2022The aim of this paper is to review mechanisms and solutions for nasal drug delivery. Literature survey was performed via PubMed, Google Scholar, Google, and ProQuest... (Review)
Review
The aim of this paper is to review mechanisms and solutions for nasal drug delivery. Literature survey was performed via PubMed, Google Scholar, Google, and ProQuest Central database of Kirikkale University. The nasal lining presents a large area of endothelium of variable permeability and with a rich vascular supply. Advantages of this route include eliminating first-pass metabolism and being easily accessible. The nasal route enables some agents which are otherwise difficult to administer to enter the systemic circulation, for example, low molecular mass compounds with high polarity, peptides, or proteins. There are three principal factors that influence the extent to which drugs can be absorbed through the nasal lining, namely the physico-chemical characteristics of the drug molecule itself, the action of the mucociliary system within the nose, and the presence of any factors increasing nasal absorption. A key factor limiting the use of the intranasal route of administration is insufficient absorption through the nasal mucosa. A number of drugs in development cannot be administered intranasally because their bioavailability following nasal administration is too low. There has been considerable research focus on methods to enhance absorption via the nasal mucosa. In this chapter, we review the literature related to this problem and discuss potential solutions.
Topics: Humans; Administration, Intranasal; Drug Delivery Systems; Nasal Mucosa; Pharmaceutical Preparations; Biological Availability
PubMed: 36524914
DOI: 10.26355/eurrev_202212_30487 -
International Journal of Molecular... Jan 2022Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous... (Review)
Review
Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.
Topics: Animals; Drug Administration Routes; Drug Compounding; Humans; Models, Animal; Neuropeptides; Organ Specificity; Regeneration; Substance P; Wound Healing
PubMed: 35054936
DOI: 10.3390/ijms23020750 -
Advanced Drug Delivery Reviews Dec 2020Micro and nanoscale drug carriers must navigate through a plethora of dynamic biological systems prior to reaching their tissue or disease targets. The biological... (Review)
Review
Micro and nanoscale drug carriers must navigate through a plethora of dynamic biological systems prior to reaching their tissue or disease targets. The biological obstacles to drug delivery come in many forms and include tissue barriers, mucus and bacterial biofilm hydrogels, the immune system, and cellular uptake and intracellular trafficking. The biointerface of drug carriers influences how these carriers navigate and overcome biological barriers for successful drug delivery. In this review, we examine how key material design parameters lead to dynamic biointerfaces and improved drug delivery across biological barriers. We provide a brief overview of approaches used to engineer key physicochemical properties of drug carriers, such as morphology, surface chemistry, and topography, as well as the development of dynamic responsive materials for barrier navigation. We then discuss essential biological barriers and how biointerface engineering can enable drug carriers to better navigate and overcome these barriers to drug delivery.
Topics: Biomedical Engineering; Blood-Brain Barrier; Chemistry, Pharmaceutical; Drug Administration Routes; Drug Carriers; Humans; Hydrogels; Mucus; Nanoparticles; Particle Size; Skin Absorption; Surface Properties; Tight Junctions
PubMed: 32535139
DOI: 10.1016/j.addr.2020.06.007 -
Advances in Wound Care Oct 2022By 2030, there will be >4 million radiation-treated cancer survivors living in the United States. Irradiation triggers inflammation, fibroblast activation, and...
By 2030, there will be >4 million radiation-treated cancer survivors living in the United States. Irradiation triggers inflammation, fibroblast activation, and extracellular matrix deposition in addition to reactive oxygen species generation, leading to a chronic inflammatory response. Radiation-induced fibrosis (RIF) is a progressive pathology resulting in skin pigmentation, reduced elasticity, ulceration and dermal thickening, cosmetic deformity, pain, and the need for reconstructive surgery. Deferoxamine (DFO) is a U.S. Food and Drug Administration (FDA)-approved iron chelator for blood dyscrasia management, which has been found to be proangiogenic, to decrease free radical formation, and reduce cell death. DFO has shown great promise in the treatment and prophylaxis of RIF in preclinical studies. Systemic DFO has a short half-life and is cumbersome to deliver to patients intravenously. Transdermal DFO delivery is complicated by its high atomic mass and hydrophilicity, preventing stratum corneum penetration. A transdermal drug delivery system was developed to address these challenges, in addition to a strategy for topical administration. DFO has great potential to translate from bench to bedside. An important step in translation of DFO for RIF prophylaxis is to ensure that DFO treatment does not affect the efficacy of radiation therapy. Furthermore, after an initial plethora of studies reporting DFO treatment by intravenous and subcutaneous routes, a significant advantage of recent studies is the success of transdermal and topical delivery. Given the strong foundation of basic scientific research supporting the use of DFO treatment on RIF, clinicians will be closely following the results of the ongoing human studies.
Topics: Administration, Cutaneous; Administration, Topical; Chelating Agents; Deferoxamine; Fibrosis; Humans
PubMed: 34074152
DOI: 10.1089/wound.2021.0021 -
BioDrugs : Clinical Immunotherapeutics,... Mar 2021The subcutaneous route of administration has provided convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion, but there is... (Review)
Review
The subcutaneous route of administration has provided convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion, but there is potential for enhanced immunogenicity toward subcutaneously administered proteins in a subset of patients. Unwanted anti-drug antibody response toward proteins or monoclonal antibodies upon repeated administration is shown to impact the pharmacokinetics and efficacy of multiple biologics. Unique immunogenicity challenges of the subcutaneous route have been realized through various preclinical and clinical examples, although subcutaneous delivery has often demonstrated comparable immunogenicity to intravenous administration. Beyond route of administration as a treatment-related factor of immunogenicity, certain product-related risk factors are particularly relevant to subcutaneously administered proteins. This review attempts to provide an overview of the mechanism of immune response toward proteins administered subcutaneously (subcutaneous proteins) and comments on product-related risk factors related to protein structure and stability, dosage form, and aggregation. A two-wave mechanism of antigen presentation in the immune response toward subcutaneous proteins is described, and interaction with dynamic antigen-presenting cells possessing high antigen processing efficiency and migratory activity may drive immunogenicity. Mitigation strategies for immunogenicity are discussed, including those in general use clinically and those currently in development. Mechanistic insights along with consideration of risk factors involved inspire theoretical strategies to provide antigen-specific, long-lasting effects for maintaining the safety and efficacy of therapeutic proteins.
Topics: Administration, Intravenous; Antibodies, Monoclonal; Antigen-Presenting Cells; Antigens; Humans; Injections, Subcutaneous
PubMed: 33523413
DOI: 10.1007/s40259-020-00465-4