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Journal of Pharmaceutical Sciences Jan 2021Pulmonary delivery has gained increased interests over the past few decades. For respiratory conditions, targeted drug delivery directly to the site of action can... (Review)
Review
Pulmonary delivery has gained increased interests over the past few decades. For respiratory conditions, targeted drug delivery directly to the site of action can achieve a high local concentration for efficacy with reduced systemic exposure and adverse effects. For systemic conditions, the unique physiology of the lung evolutionarily designed for rapid gaseous exchange presents an entry route for systemic drug delivery. Although the development of inhaled formulations has come a long way over the last few decades, many aspects of it remain to be elucidated. In particular, a reliable and well-understood method for in vitro-in vivo correlations remains to be established. With the rapid and ongoing advancement of technology, there is much potential to better utilise computational methods including different types of modelling and simulation approaches to support inhaled formulation development. This review intends to provide an introduction on some fundamental concepts in pulmonary drug delivery and inhaled formulation development followed by discussions on some challenges and opportunities in the translation of inhaled pharmaceuticals from preclinical studies to clinical development. The review concludes with some recent advancements in modelling and simulation approaches that could play an increasingly important role in modern formulation development of inhaled pharmaceuticals.
Topics: Administration, Inhalation; Computer Simulation; Drug Delivery Systems; Lung; Pharmaceutical Preparations
PubMed: 32916138
DOI: 10.1016/j.xphs.2020.09.006 -
Human Vaccines & Immunotherapeutics May 2022Skin cancers are among the most physically accessible malignancies, so local delivery of a medication into the tumor, so-called intratumoral therapy, is an appealing... (Review)
Review
Skin cancers are among the most physically accessible malignancies, so local delivery of a medication into the tumor, so-called intratumoral therapy, is an appealing route of drug administration. Intratumoral therapies have the potential to increase local drug concentration and/or attract immune cells to the local tumor microenvironment, possibly with fewer systemic side effects. A wide array of intratumoral agents have been studied to date in patients with advanced melanoma, including chemotherapeutic drugs, immune modulating agents, and cancer-directed vaccines. In this review, we will summarize the key pre-clinical and clinical data supporting the use of intratumoral therapy for advanced unresectable and metastatic melanoma. First, we will discuss the history of intratumoral immunotherapy for the treatment of melanoma and the various agents studied to date. Second, we will explore how intratumoral therapies can constitute an in situ vaccine, potentially leading to disease control both locally and systemically. Finally, we will highlight opportunities in the field and key future directions.
Topics: Cancer Vaccines; Humans; Immunotherapy; Injections, Intralesional; Melanoma; Tumor Microenvironment; Vaccination
PubMed: 35559766
DOI: 10.1080/21645515.2021.1890512 -
European Journal of Pharmaceutics and... Mar 2023Cutaneous melanoma (CM) is a multifactorial disease whose treatment still presents challenges: the rapid progression to advanced CM, which leads to frequent recurrences... (Review)
Review
Cutaneous melanoma (CM) is a multifactorial disease whose treatment still presents challenges: the rapid progression to advanced CM, which leads to frequent recurrences even after surgical excision and, notably, the low response rates and resistance to the available therapies, particularly in the case of unresectable metastatic CM. Thereby, alternative innovative therapeutic approaches for CM continue to be searched. In this review we discuss relevant preclinical research studies, and provide a broad-brush analysis of patents and clinical trials which involve the application of nanotechnology-based delivery systems in CM therapy. Nanodelivery systems have been developed for the delivery of anticancer biomolecules to CM, which can be administered by different routes. Overall, nanosystems could promote technological advances in several therapeutic modalities and can be used in combinatorial therapies. Nevertheless, the results of these preclinical studies have not been translated to clinical applications. Thus, concerted and collaborative research studies involving basic, applied, translational, and clinical scientists need to be performed to allow the development of effective and safe nanomedicines to treat CM.
Topics: Humans; Melanoma; Skin Neoplasms; Nanoparticle Drug Delivery System; Administration, Cutaneous; Melanoma, Cutaneous Malignant
PubMed: 36773725
DOI: 10.1016/j.ejpb.2023.02.002 -
Advanced Drug Delivery Reviews Apr 2021Intercellular tight junctions represent a formidable barrier against paracellular drug absorption at epithelia (e.g., nasal, intestinal) and the endothelium (e.g.,... (Review)
Review
Intercellular tight junctions represent a formidable barrier against paracellular drug absorption at epithelia (e.g., nasal, intestinal) and the endothelium (e.g., blood-brain barrier). In order to enhance paracellular transport of drugs and increase their bioavailability and organ deposition, active excipients modulating tight junctions have been applied. First-generation of permeation enhancers (PEs) acted by unspecific interactions, while recently developed PEs address specific physiological mechanisms. Such target specific tight junction modulators (TJMs) have the advantage of a defined specific mechanism of action. To date, merely a few of these novel active excipients has entered into clinical trials, as their lack in safety and efficiency in vivo often impedes their commercialisation. A stronger focus on the development of such active excipients would result in an economic and therapeutic improvement of current and future drugs.
Topics: Animals; Drug Administration Routes; Drug Delivery Systems; Humans; Tight Junctions
PubMed: 33617902
DOI: 10.1016/j.addr.2021.02.008 -
South African Medical Journal =... Dec 2023Oral drug formulations and enteral feeds may inadvertently be administered intravenously. Intravenous medications may be inadvertently administered intra-arterially.... (Review)
Review
Oral drug formulations and enteral feeds may inadvertently be administered intravenously. Intravenous medications may be inadvertently administered intra-arterially. These examples of wrong-route drug administration errors have the potential to cause significant organ dysfunction and even death. This narrative review aims to explore the pathophysiological mechanisms underlying such errors and investigate preventive strategies and potential therapeutic options.
Topics: Humans; South Africa; Medication Errors; Administration, Intravenous
PubMed: 38525634
DOI: 10.7196/SAMJ.2023.v113i12.1043 -
Journal of Neuroimmune Pharmacology :... Mar 2021The development of novel antiretroviral treatments has led to a significant turning point in the fight against HIV. Although therapy leads to virologic suppression and... (Review)
Review
The development of novel antiretroviral treatments has led to a significant turning point in the fight against HIV. Although therapy leads to virologic suppression and prolonged life expectancies, HIV-associated neurocognitive disorder (HAND) remains prevalent. While various hypotheses have been proposed to explain this phenomenon, a growing body of literature explores the neurotoxic effects of antiretroviral therapy. Research to date brings into question the potential role of such medications in neurocognitive and neuropsychiatric impairment seen in HIV-positive patients. This review highlights recent findings and controversies in cellular, molecular, and clinical neurotoxicity of antiretrovirals. It explores the pathogenesis of such toxicity and relates it to clinical manifestations in each medication class. The concept of accelerated aging in persons living with HIV (PLWH) as well as potential treatments for HAND are also discussed. Ultimately, this article hopes to educate clinicians and basic scientists about the neurotoxic effects of antiretrovirals and spur future scientific investigation into this important topic. Graphical Abstract.
Topics: AIDS Dementia Complex; Aging; Anti-HIV Agents; Blood-Brain Barrier; Central Nervous System Diseases; Drug Administration Routes; Drug Interactions; HIV Infections; Humans; Neurocognitive Disorders
PubMed: 31823251
DOI: 10.1007/s11481-019-09886-7 -
The Journal of Pharmacology and... Sep 2019Advanced drug delivery technologies, in general, enable drug reformulation and administration routes, together contributing to life-cycle management and allowing the... (Review)
Review
Advanced drug delivery technologies, in general, enable drug reformulation and administration routes, together contributing to life-cycle management and allowing the innovator to maintain the product monopoly. Over the years, there has been a steady shift from mere life-cycle management to drug repurposing-applying delivery technologies to tackle solubility and permeability issues in early stages or safety and efficacy issues in the late stages of drug discovery processes. While the drug and the disease in question primarily drive the choice of route of administration, the oral route, for its compliance and safety attributes, is the most preferred route, particularly when it comes to chronic conditions, including pain, which is not considered a disease but a symptom of a primary cause. Therefore, the attempt of this review is to take a stock of the advances in oral delivery technologies that are applicable for injectable to oral transformation, improve risk-benefit profiles of existing orals, and apply them in the early discovery program to minimize the drug attrition rates.
Topics: Administration, Oral; Animals; Capsules; Drug Carriers; Drug Delivery Systems; Humans; Nanomedicine; Tablets
PubMed: 31010845
DOI: 10.1124/jpet.118.255828 -
Journal of Controlled Release :... Oct 2020Pulmonary delivery of lipid-based nanotherapeutics by inhalation presents an advantageous alternative to oral and intravenous routes of administration that avoids... (Review)
Review
Pulmonary delivery of lipid-based nanotherapeutics by inhalation presents an advantageous alternative to oral and intravenous routes of administration that avoids enzymatic degradation in gastrointestinal tract and hepatic first pass metabolism and also limits off-target adverse side effects upon heathy tissues. For lung-related indications, inhalation provides localized delivery in order to enhance therapeutic efficacy at the site of action. Optimization of physicochemical properties, selected drug and inhalation format can greatly influence the pharmacokinetic behavior of inhaled nanoparticle systems and their payloads. The present review analyzes a wide range of nanoparticle systems, their formulations and consequent effect on pharmacokinetic distribution of delivered active components after inhalation.
Topics: Administration, Inhalation; Drug Compounding; Drug Delivery Systems; Lung; Nanoparticles
PubMed: 32681948
DOI: 10.1016/j.jconrel.2020.07.011 -
Pharmaceutical Research Dec 2019Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. While this route is an easy to... (Review)
Review
Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. While this route is an easy to master, quick, suitable for chronic treatments and with low impact of stress on laboratory rodents, there is a common concern that it may not be an acceptable route for drug administration in experimental studies. The latter is likely due to sparsity of information regarding pharmacokinetics of pharmacological agents and the mechanisms through which agents get systemic exposure after IP administration. In this review, we summarize the main mechanisms involved in bioavailability of IP administered drugs and provide examples of pharmacokinetic profiles for small and large molecules in comparison to other routes of administration. We conclude with a notion that IP administration of drugs in experimental studies involving rodents is a justifiable route for pharmacological and proof-of-concept studies where the goal is to evaluate the effect(s) of target engagement rather than properties of a drug formulation and/or its pharmacokinetics for clinical translation.
Topics: Animals; Biological Availability; Drug Administration Routes; Drug Compounding; Humans; Injections, Intraperitoneal; Injections, Subcutaneous; Models, Animal; Particle Size; Pharmaceutical Preparations; Pharmacokinetics; Signal Transduction
PubMed: 31873819
DOI: 10.1007/s11095-019-2745-x -
JPMA. the Journal of the Pakistan... Aug 2021Proteins and peptide drugs have a great therapeutic potential and their usage in the treatment of various severe diseases has revolutionised the fields of... (Review)
Review
Proteins and peptide drugs have a great therapeutic potential and their usage in the treatment of various severe diseases has revolutionised the fields of pharmaceuticals and biotechnology. For successful therapeutic effects, various efforts have been made for effective delivery of proteins/peptide drugs through various routes of administrations. Parenteral and non-parenteral drug deliveries are regarded as significant routes of drug absorption. In addition to intravenous, subcutaneous and intramuscular routes, the oral route is more effective for protein and peptides therapeutics. However, there is a need to improve non-parenteral drug delivery systems (DDS) to increase drug absorption in a more effective way. The present narrative review was planned to describe routes and barriers for protein/peptide drugs and how to improve drug delivery systems in an effective way. For this purpose, numerous research articles were searched from year 2000-2021 using search engines like PubMed, Google Scholar, Medline and ISI Web of Knowledge, and Bioline International while applying different keywords such as 'protein and peptide drugs', 'drug delivery systems', 'parenteral and non-parenteral routes of drug delivery' and 'physicochemical barriers'. It was concluded that the success of the therapeutics is strongly influenced by the differential delivery of targeted antigen, the choice of targeting protein or peptide, and drug-release characteristics of the linker used. Furthermore, there should be an improvement in non-parenteral DDSs so that the drugs might be administered in an appropriate manner.
Topics: Administration, Oral; Drug Delivery Systems; Humans; Peptides; Proteins
PubMed: 34418025
DOI: 10.47391/JPMA.759