scholarly journals Intranasal drug delivery: opportunities and toxicologic challenges during drug development

2021 ◽  
Author(s):  
Lea-Adriana Keller ◽  
Olivia Merkel ◽  
Andreas Popp
Keyword(s):  
Drug Delivery ◽  
Drug Development ◽  
Targeted Delivery ◽  
Nasal Delivery ◽  
Systemic Delivery ◽  
Onset Of Action ◽  
Physiological Basis ◽  
Intranasal Drug Delivery ◽  
Non Invasive ◽  
Approved Drugs

Abstract Over the past 10 years, the interest in intranasal drug delivery in pharmaceutical R&D has increased. This review article summarises information on intranasal administration for local and systemic delivery, as well as for CNS indications. Nasal delivery offers many advantages over standard systemic delivery systems, such as its non-invasive character, a fast onset of action and in many cases reduced side effects due to a more targeted delivery. There are still formulation limitations and toxicological aspects to be optimised. Intranasal drug delivery in the field of drug development is an interesting delivery route for the treatment of neurological disorders. Systemic approaches often fail to efficiently supply the CNS with drugs. This review paper describes the anatomical, histological and physiological basis and summarises currently approved drugs for administration via intranasal delivery. Further, the review focuses on toxicological considerations of intranasally applied compounds and discusses formulation aspects that need to be considered for drug development. Graphical abstract

scholarly journals Multiplexed Non-invasive in vivo Imaging to Assess Metabolism and Receptor Engagement in Tumor Xenografts

2019 ◽  
Author(s):  
Alena Rudkouskaya ◽  
Nattawut Sinsuebphon ◽  
Marien Ochoa ◽  
Joe E. Mazurkiewicz ◽  
Xavier Intes ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Metabolic Response ◽  
Imaging Modalities ◽  
Wide Field ◽  
Receptor Ligand ◽  
Non Invasive ◽  
Intracellular Drug Delivery

AbstractFollowing an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. To date, non-invasive quantitative imaging modalities that can comprehensively assess simultaneous cellular drug delivery efficacy and therapeutic response are lacking. In this regard, Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in vivo and subsequent intracellular internalization, which is critical to assess the delivery efficacy of targeted therapeutics. However, implementation of multiplexing optical imaging with FRET in vivo is challenging to achieve due to spectral crowding and cross-contamination. Herein, we report on a strategy that relies on a dark quencher that enables simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700) using in vitro NIR FLI microscopy and in vivo wide-field MFLI imaging. Second, we report on simultaneous in vivo imaging of the metabolic probe IRDye 800CW 2-deoxyglucose (2-DG) and MFLI-FRET imaging of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies.

scholarly journals Pulmonary Delivery of Biological Drugs

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1025
Author(s):  
Wanling Liang ◽  
Harry W. Pan ◽  
Driton Vllasaliu ◽  
Jenny K. W. Lam
Keyword(s):  
Pulmonary Delivery ◽  
High Specificity ◽  
Therapeutic Modality ◽  
Systemic Delivery ◽  
Biological Drugs ◽  
Onset Of Action ◽  
Non Invasive ◽  
Inhalation Devices ◽  
Rapid Absorption ◽  
Immense Potential

In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by parenteral injection (with a very few exceptions). Pulmonary delivery is an attractive non-invasive alternative route of administration for local and systemic delivery of biologics with immense potential to treat various diseases, including diabetes, cystic fibrosis, respiratory viral infection and asthma, etc. The massive surface area and extensive vascularisation in the lungs enable rapid absorption and fast onset of action. Despite the benefits of pulmonary delivery, development of inhalable biological drug is a challenging task. There are various anatomical, physiological and immunological barriers that affect the therapeutic efficacy of inhaled formulations. This review assesses the characteristics of biological drugs and the barriers to pulmonary drug delivery. The main challenges in the formulation and inhalation devices are discussed, together with the possible strategies that can be applied to address these challenges. Current clinical developments in inhaled biological drugs for both local and systemic applications are also discussed to provide an insight for further research.

Virtual Assessment of the Performance of an Inhalation Drug Delivery Device

2007 ◽  
Author(s):  
Françoise Dufour ◽  
Gavin Davies
Keyword(s):  
Drug Delivery ◽  
Nasal Delivery ◽  
Pharmaceutical Aerosols ◽  
Drug Delivery Device ◽  
Non Invasive ◽  
Optimal Drug ◽  
Drug Dispersion ◽  
Computational Fluid Dynamics Cfd ◽  
Inhaler Devices ◽  
Inhaled Medication

Inhalation therapies are gaining popularity for both respiratory and non-respiratory therapies. However the challenge remains to achieve optimal drug delivery because of the complex interaction between inhaler devices, drug formulations along with patients’ coordination and physiology. In order to lower R&D costs and efforts, and understand better the mechanics of pharmaceutical aerosols, system designers are looking for comprehensive tools enabling them to reproduce virtual inhalation processes. Computational fluid dynamics (CFD) techniques represent a non-invasive way of predicting the fate of inhaled medication from oral or nasal delivery devices. The object of this work is to apply CFD methodology to model the full inhalation mechanism, from the drug dispersion inside the device and delivery to the patient, to its journey within the respiratory tract.

scholarly journals Localized and targeted delivery of NSAIDs for treatment of inflammation: A review

2018 ◽  
Vol 244 (6) ◽  
pp. 433-444 ◽  
Author(s):  
Rebecca M Haley ◽  
Horst A von Recum
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Local Drug Delivery ◽  
Future Research ◽  
Systemic Delivery ◽  
Number Of Patients ◽  
Long Term Treatment ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Inflammatory processes are increasingly being identified at the core of many different disease states (e.g. heart disease, cancer, diabetes). As such, anti-inflammatory strategies available through drug delivery have undergone renewed interest. Due to the systemic side effects of steroidal drugs, non-steroidal anti-inflammatory drugs are often preferred for long-term treatment of inflammation in a variety of applications. While non-steroidal anti-inflammatory drugs are generally safe, there are some serious side effects that can be associated with their usage, particularly when given systemically or orally. Due to the high number of patients taking non-steroidal anti-inflammatory drugs, the reduction or elimination of these side effects, such as is possible through local drug delivery, could have a very powerful effect on patient quality of life. This review comments on a sampling of existing methods for localized or targeted delivery of non-steroidal anti-inflammatory drugs, with the goal of helping future research groups to focus on bettering methods shown to be effective and filling the gaps of knowledge in this field. Additionally, commentary is made on the field as a whole, and the standardization issues that arise from its expansiveness and diversity. Impact statement This work provides an overview of research currently being done exploring potential drug delivery device strategies for NSAIDs as an alternative to systemic delivery. Commentary on this field is made in an attempt to aid future experimental design, enabling researchers to determine the drugs and delivery vehicles which are most advantageous for them to pursue, as well as suggestions to standardize the reporting of such future research.

NON INVASIVE DELIVERY OF PROTEIN AND PEPTIDE DRUGS: A REVIEW

2017 ◽  
Vol 10 (8) ◽  
pp. 25 ◽  
Author(s):  
P.k. Lakshmi ◽  
D Prasanthi ◽  
B Veeresh
Keyword(s):  
Drug Delivery ◽  
Drug Transport ◽  
Local Treatment ◽  
Oral Formulation ◽  
Systemic Delivery ◽  
Peptide Drugs ◽  
Administration Routes ◽  
Treatment Regimens ◽  
Non Invasive ◽  
Proteins And Peptides

Till recent, injections remained the most common route for administration of protein and peptide drugs because of their poor bioavailability in the other routes. Because it is generally recognized that injection based delivery is a major impediment to the commercial success of therapeutic proteins and peptides, research in both academia and industry continues to focus on ways to overcome this problem. Possible non-parenteral administration routes for delivery of peptide and protein drugs include oral, nasal, ocular, transdermal, rectal, colonic, and vaginal route. The large surface area associated with most of these routes makes them attractive targets for drug delivery. While non-invasive administration by these routes is considered a more logical and achievable option for local treatment regimens, systemic delivery of proteins and peptides is significantly more challenging. In spite of effort made on the development of drugs for these routes, most of the successes fail to address how the technology will be transformed to a commercial product. The only notable exceptions have been the successful commercialization of nasal formulations for systemic delivery of a limited number of therapeutic peptides, and recent regulatory approvals of both pulmonary and buccal delivery systems for systemic delivery of insulin and an oral formulation of a small peptide analog, cyclosporine, have been commercialized. The present review aims to discuss the potential non-invasive routes of protein and peptide drug delivery. The factors which will affect drug transport and the bioavailability of proteins administered through these routes is also emphasized

scholarly journals Lipid Nanoparticles as Carriers for Bioactive Delivery

2021 ◽  
Vol 9 ◽  
Author(s):  
Neerupma Dhiman ◽  
Rajendra Awasthi ◽  
Bhupesh Sharma ◽  
Harsha Kharkwal ◽  
Giriraj T. Kulkarni
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Lipid Nanoparticles ◽  
Delivery Systems ◽  
Bioactive Molecules ◽  
Nanodrug Delivery ◽  
Solid Lipid ◽  
Nanostructure Lipid Carriers ◽  
Approved Drugs

Nanotechnology has made a great impact on the pharmaceutical, biotechnology, food, and cosmetics industries. More than 40% of the approved drugs are lipophilic and have poor solubility. This is the major rate-limiting step that influences the release profile and bioavailability of drugs. Several approaches have been reported to administer lipophilic drugs with improved solubility and bioavailability. Nanotechnology plays a crucial role in the targeted delivery of poorly soluble drugs. Nanotechnology-based drug delivery systems can be classified as solid lipid nanoparticulate drug delivery systems, emulsion-based nanodrug delivery systems, vesicular drug delivery systems, etc. Nanotechnology presents a new frontier in research and development to conquer the limitations coupled with the conventional drug delivery systems through the formation of specific functionalized particles. This review presents a bird's eye view on various aspects of lipid nanoparticles as carriers of bioactive molecules that is, synthesis, characterization, advantage, disadvantage, toxicity, and application in the medical field. Update on recent development in terms of patents and clinical trials of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) have also been discussed in this article.

scholarly journals Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

2021 ◽  
Vol 22 (17) ◽  
pp. 9118
Author(s):  
Wentao Xia ◽  
Zixuan Tao ◽  
Bin Zhu ◽  
Wenxiang Zhang ◽  
Chang Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Targeted Delivery ◽  
Slow Release ◽  
Therapeutic Strategies ◽  
Early Diagnostics ◽  
Non Invasive ◽  
Innovative Methods ◽  
Nano Drug Delivery ◽  
Polymer Nanocarriers

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.

scholarly journals Sublingual Tablets : An Overview

2019 ◽  
pp. 181-187
Author(s):  
Rohit S. Nikam ◽  
Rahul P. Jadhav ◽  
Dr. Prakash D. Jadhav ◽  
Vishal D. Yadav
Keyword(s):  
Drug Delivery ◽  
Rapid Onset ◽  
Oral Route ◽  
Dosage Forms ◽  
Peroral Administration ◽  
Systemic Delivery ◽  
Onset Of Action ◽  
Promising Alternative ◽  
Evaluation Parameters ◽  
Pass Metabolism

<p>Drug delivery via the oral mucous membrane is considered to be a promising alternative to the oral route. Sublingual route is a rapid onset of action and better patient compliance than orally ingested tablets. Sublingual literally meaning is 'under the tongue', administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. Peroral administration of drug has disadvantages such as Hepatic first pass metabolism and enzymatic degradation within the GI tract that limits oral administration of certain classes of drug like peptides and proteins. So, other absorptive mucosa is considered as potential sites for drug administration. Trans-mucosal routes of drug delivery (i.e. the mucosal linings of the nasal, rectal, vaginal, ocular, and oral cavity) offer several advantages over peroral administration for systemic delivery. This review highlights the sublingual dosage forms for the treatment of migraine, advantages, Disadvantages, various evaluation parameters and commercially available sublingual dosage forms.</p>

scholarly journals Primary and Novel Approaches in Colon Targeted Drug Delivery System: A Review

2015 ◽  
Vol 3 (02) ◽  
pp. 37-57
Author(s):  
Komal . ◽  
Ujjwal Nautiyal ◽  
Ramandeep , Anita Devi Singh ◽  
Anita Devi
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Local Treatment ◽  
Systemic Delivery ◽  
Colonic Delivery ◽  
Targeted Drug ◽  
Targeted Drug Delivery System

Targeted drug delivery into the colon is highly desirable for local treatment of a variety of bowel diseases such as ulcerative colitis, Crohn’s disease, amoeabiasis , colonic cancer, local treatment of colonic pathologies, and systemic delivery of protein and peptide drugs. Colonic delivery refers to targeted delivery of drugs into the lower GI tract, which occurs primarily in the large intestine (i.e. colon). The colon specific drug delivery system (CDDS) should be capable of protecting the drug en route to the colon i.e. drug release and absorption should not occur in the stomach as well as the small intestine, and neither the bioactive agent should be degraded in either of the dissolution sites but only released and absorbed once the system reaches the colon. Different approaches are designed based on prodrug formulation, pHsensitivity, time-dependency (lag time), microbial degradation and osmotic pressure etc to formulate the different dosage forms like tablets, capsules, multiparticulates, microspheres, liposomes for colon targeting. The efficiency of drug delivery system is evaluated using different in vitro and in vivo release studies. This review article discusses, in brief, introduction to targeted drug delivery system, anatomy and physiology of the colon and approaches utilized in the colon targeted drug delivery system.

scholarly journals Innovative approach for nasal drug delivery system for brain target

2021 ◽  
Vol 9 (3) ◽  
pp. 093-106
Author(s):  
Priyadarshani G Patil ◽  
Sampada V Marodkar ◽  
Sachin J Dighade ◽  
Prajakta N Dongare ◽  
Bhagyashri A Borade
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Blood Brain Barrier ◽  
Delivery System ◽  
Drug Transport ◽  
Nasal Delivery ◽  
Brain Barrier ◽  
Non Invasive ◽  
Brain Drug Delivery ◽  
Blood Brain

The goal of brain drug targeting technology is the delivery of therapeutics across the blood brain barrier (BBB), including the human BBB. Nose to brain drug delivery has received a great deal of attention as a non- invasive, convenient and reliable drug delivery system. For the systemic and targetedadministration of drug. The various drug deliveries through some drug transport pathways, Factor influencing nasal drug absorption, formulation strategies nose to brain, colloidal carriers in nose to brain drug delivery system and nasal delivery systems. Physiological barriers (BBB) that restricts the delivery of drug to CNS. Thus intranasal route has attracted a wide attention of convenient, non-invasive, reliable, and safe route to achieve faster and higher level of drug in the brain through olfactory region by passing blood brain barrier. Intranasal administration rapid onset of action, no first –pass effect , no gastrointestinal degradation lungs toxicity and non-invasiveness application and also improves bioavailability.

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