Frontiers in drug delivery最新文献

{"title":"Role of microRNAs in the regulation of blood-brain barrier function in ischemic stroke and under hypoxic conditions in vitro","authors":"Aili Sun, Kinga G. Blecharz-Lang, A. Małecki, P. Meybohm, M. Nowacka-Chmielewska, M. Burek","doi":"10.3389/fddev.2022.1027098","DOIUrl":"https://doi.org/10.3389/fddev.2022.1027098","url":null,"abstract":"The blood-brain barrier (BBB) is a highly specialized structure that separates the brain from the blood and allows the exchange of molecules between these two compartments through selective channels. The breakdown of the BBB is implicated in the development of severe neurological diseases, especially stroke and traumatic brain injury. Oxygen-glucose deprivation is used to mimic stroke and traumatic brain injury in vitro. Pathways that trigger BBB dysfunction include an imbalance of oxidative stress, excitotoxicity, iron metabolism, cytokine release, cell injury, and cell death. MicroRNAs are small non-coding RNA molecules that regulate gene expression and are emerging as biomarkers for the diagnosis of central nervous system (CNS) injuries. In this review, the regulatory role of potential microRNA biomarkers and related therapeutic targets on the BBB is discussed. A thorough understanding of the potential role of various cellular and linker proteins, among others, in the BBB will open further therapeutic options for the treatment of neurological diseases.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41624323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesh nebulizers enabling transnasal pulmonary delivery of medical aerosols to infants and toddlers: Roles, challenges, and opportunities","authors":"Arzu Ari, B. Rubin, J. Fink","doi":"10.3389/fddev.2022.995489","DOIUrl":"https://doi.org/10.3389/fddev.2022.995489","url":null,"abstract":"The development of mesh nebulizer technology has expanded the ability to deliver medical aerosols to infants and small children via nasal cannula and prongs. Mesh nebulizers do not require compressed gas to generate aerosols and have a smaller, lighter profile facilitating placement in delivery circuits, unlike ultrasonic nebulizers. Prior to this century, aerosol delivery with the nasal interface to 1–4 kg infants or surrogate animal models was limited to low single-digit deposition. In vitro and animal studies with the enabling mesh technology increase inhaled dose by upwards of 14% when nasal continuous positive airway pressure ventilation is in use. Recently, investigations of transnasal aerosol delivery to the lung have expanded to include nasal cannula interfaces with both high and low flow oxygen administration, nasal continuous positive airway pressure therapy, and nasal noninvasive ventilation in treating respiratory distress, respiratory insufficiency, and acute respiratory failure of infants and toddlers. We will first examine the progression of testing transpulmonary delivery of medical aerosols from in vitro models to in vivo animal and human studies. Then, we will explain current and developing applications in clinical practice to view future directions and opportunities.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44666112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?","authors":"E. D. del Amo","doi":"10.3389/fddev.2022.954771","DOIUrl":"https://doi.org/10.3389/fddev.2022.954771","url":null,"abstract":"Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43447845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing the design and dosing of dry powder inhaler formulations of the cationic liposome adjuvant CAF®01 for pulmonary immunization","authors":"Aneesh Thakur, You Xu, G. Cano-Garcia, Siqi Feng, Fabrice Rose, P. Gerde, P. Andersen, D. Christensen, C. Foged","doi":"10.3389/fddev.2022.973599","DOIUrl":"https://doi.org/10.3389/fddev.2022.973599","url":null,"abstract":"Thermostability is one of the product characteristics preferred by WHO for vaccines against respiratory infections due to ease of administration, pain minimization, and low costs. Thermostable dry powder inhaler (DPI) vaccine formulations can induce protective antibodies and T cells at the site of infection in the lungs. However, the majority of licensed human vaccines is based on liquid dosage forms, and there is no licensed mucosal adjuvants. The cationic adjuvant formulation 01 (CAF®01) is a liposome-based adjuvant system that (i) induces robust T cells and antibodies, (ii) is safe and well-tolerated in clinical trials, and (iii) induces mucosal immune responses after pulmonary administration. However, the optimal DPI formulations of CAF®01 for pulmonary immunization are not known. Here, we show that DPI formulations of CAF®01 spray-dried with a combination of sugars and the amino acid leucine exhibit optimal aerosolization properties and distribute in the lung lobes upon pulmonary administration. We demonstrate that the type of amorphous sugar used as stabilizer and the amount (w/w) of leucine used during spray drying affect the physicochemical properties and aerosol performance of DPI formulations. By systematically varying the ratios (w/w) of trehalose, dextran and leucine used as excipients during spray drying, we manufactured DPI formulations of CAF®01 that displayed (i) a spherical or wrinkled surface morphology, (ii) an aerodynamic diameter and particle size distribution optimal for deep lung deposition, and (iii) solid-state and aerosolization properties suitable for lung delivery. Using a design-of-experiments-based approach, we identified the most optimal process parameters in an in vivo aerosol generator, i.e., the PreciseInhale® system, which was used to measure the flowability of the aerosols. We found that the DPI formulation of CAF®01 spray-dried with trehalose and dextran (70% w/w) and leucine (30% w/w) displayed the most optimal physicochemical, morphological, solid-state, and aerosolization properties for deep lung deposition. Upon pulmonary administration, this DPI formulation distributed in the lung lobes in a way that was almost identical to the biodistribution of the non-spray dried formulation. Hence, DPI formulations of CAF®01, prepared with trehalose and dextran sugar matrix and a leucine shell, display physicochemical and aerosol properties suitable for inhalation.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49034327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances and future prospective of topical and transdermal delivery systems","authors":"Pronalis Tapfumaneyi, M. Imran, Yousuf H. Mohammed, M. S. Roberts","doi":"10.3389/fddev.2022.957732","DOIUrl":"https://doi.org/10.3389/fddev.2022.957732","url":null,"abstract":"Recent advances in topical and transdermal drug delivery systems have enabled targeted delivery of therapeutics to the site of action by enhancing drug permeation across the stratum corneum and increased bioavailability. Despite various technological advancements, some dermatoses still have limited treatment options due to potential adverse effects and challenges in formulation development. To address some of the limitations posed by conventional dermatotherapy, nano-based technologies have been developed and have demonstrated a significant improvement in dermatotherapy. Their distinct physicochemical properties demonstrate their overall superior therapeutic efficacy in providing sustained and effective targeted drug release, as well as improved solubility of hydrophobic actives with optimized drug formulations. These nanocarriers are commonly classified as polymeric, lipid-based, metallic, and vesicular nanocarriers, including nanoemulsions, nanofibers, and microneedles. This mini-review aims to address recent advances in nano-based technologies, providing a brief insight on some of the current and prospective technologies and approaches aimed at improving transdermal delivery.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45099891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of three methods for assessment of drug elution: In vitro elution of gentamicin from a collagen-based scaffold","authors":"Caroline Billings, David E. Anderson","doi":"10.3389/fddev.2022.958731","DOIUrl":"https://doi.org/10.3389/fddev.2022.958731","url":null,"abstract":"In vitro drug elution experiments are commonly performed when evaluating the fitness of drug delivery devices for in vivo use. Evaluation of drug elution characteristics spans many drug delivery applications including local delivery of antimicrobials and chemotherapeutics, and is of particular interest for prevention and treatment of orthopedic infections. Despite widespread utility, there is little agreement on methodology to perform such studies, and there are recognized limitations in published works. We evaluated three of the most commonly reported in vitro drug elution methods. We utilized a commercially available collagen matrix (Fibro-Gide®, Geistlich) and an antibiotic that is widely used for local antimicrobial therapy (gentamicin). The protocols used are: 1. complete replacement of media and washing of device, 2. complete replacement of media without washing, or 3. partial replacement of media. The results show statistically significant differences in elution characteristics among the three methods utilizing this delivery vehicle and drug. These results may provide the framework for moving toward more consistent methodology for in vitro elution experiments and address certain acknowledged limitations in the literature.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47876133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines","authors":"Alyson Yamaguchi, J. van Dam, A. Dhalla, Kyle P. Horlen, M. Imran, April T. Vo, Mir Hashim","doi":"10.3389/fddev.2022.955569","DOIUrl":"https://doi.org/10.3389/fddev.2022.955569","url":null,"abstract":"Biotherapeutics such as peptides and antibodies are highly efficacious clinically but, unlike conventional medications, cannot be administered orally as they get digested and inactivated. Thus, biotherapeutics require parenteral routes for delivery, such as intravenous, intramuscular or subcutaneous administration. However, these delivery methods have limitations such as poor patient compliance or may require clinical supervision compared to oral therapies. We explored whether a novel, orally administered transenteric delivery system (Robotic Pill) could provide equivalent bioavailability to parenterally administered drugs. Utilizing an awake canine model, we demonstrated that orally administered Robotic Pills containing either human IgG or an anti-cytokine monoclonal antibody directed against either TNFα or interleukin-17A yielded bioavailability equivalent to parenterally administered controls. The ability to achieve clinically relevant blood levels of biotherapeutics via any orally administered preparation represents an important advance in drug delivery.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48297874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-Based Vaccines Against COVID-19 for Massive Vaccination in Africa","authors":"Islam El Jaddaoui, Najib Al Idrissi, S. Hamdi, L. Wakrim, C. Nejjari, S. Amzazi, Abdelatif Elouahabi, Y. Bakri, H. Ghazal","doi":"10.3389/fddev.2022.909958","DOIUrl":"https://doi.org/10.3389/fddev.2022.909958","url":null,"abstract":"During the unprecedented COVID-19 pandemic, the primary goal of many countries has been to achieve herd immunity through the organization of massive vaccination campaigns. Nevertheless, developing countries, including Africans, have been facing limited vaccine supply. Conventional inactivated or subunit vaccines are widely used across the world; however, their production is costly and could be limited by the supply chain during a pandemic such as COVID-19. Genetic vaccines, such as mRNA- or adenovirus-based vaccines, have been developed as alternatives but are still costly and require low-temperature storage. The plant-based vaccine concept has attracted increasing attention in recent years due to its potential advantages, such as low cost, high production volume, and thermostability. In this review, we propose plant-based vaccines as an attractive alternative for massive and rapid vaccination protocols against COVID-19 in African countries by exploiting local crops. In addition, we discuss the mechanisms of action, required standards, benefits, challenges, and prospects for the application of this novel biotechnological tool in the African continent.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46145326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Blood-Brain Barrier in Space: Implications for Space Travelers and for Human Health on Earth","authors":"S. Amselem, S. Eyal","doi":"10.3389/fddev.2022.931221","DOIUrl":"https://doi.org/10.3389/fddev.2022.931221","url":null,"abstract":"Astronauts have flown to space for decades, but the effects of spaceflight on human health have not been fully clarified yet. Several pathologies have only been detected after it has become customary for astronauts to spend months rather than days in space and with the advance of inflight monitoring. Examples include the neuro-ocular spaceflight associated syndrome, changes to the brain’s white matter, and, more recently, altered cerebral blood flow and related hypercoagulability. This review outlines spaceflight-induced brain disorders in astronauts and putative contributing factors. It next presents ongoing and upcoming studies of the BBB onboard space platforms. Finally, it describes how the space environment can be harnessed for improving drug-delivery across the BBB for humans both in space and on Earth.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48865335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Comparison of Breast Cancer Resistance Protein (BCRP/ABCG2) Expression and Function Between Maternal Blood-Brain Barrier and Placental Barrier in Mice at Different Gestational Ages","authors":"A. Fujita, S. Noguchi, R. Hamada, Tsutomu Shimada, Satomi Katakura, T. Maruyama, Y. Sai, T. Nishimura, M. Tomi","doi":"10.3389/fddev.2022.932576","DOIUrl":"https://doi.org/10.3389/fddev.2022.932576","url":null,"abstract":"Breast cancer resistance protein (BCRP) is expressed by brain capillary endothelial cells and at the interface between two placental syncytiotrophoblast layers in rodents and serves to suppress drug distribution to the brain and the fetus. The purpose of the present study is to determine and compare the apparent impact of a single BCRP molecule on drug transfer between the maternal blood-brain barrier and placental barrier in pregnant mice at different gestation ages. BCRP protein was quantified by liquid chromatography-tandem mass spectrometry. Genistein or dantrolene was continuously administered to pregnant Bcrp −/− or wild-type (WT) mice, and the brain-to-plasma concentration ratio in the mother (K p,brain) and the fetal-to-maternal ratio of plasma concentrations (K p,fp) were determined. At gestational day 15.5 (GD15.5), the protein amount of BCRP at the murine placental barrier was estimated to be approximately three times higher than at the maternal blood-brain barrier, but the levels were approximately the same at GD17.5 due to the decline of placental BCRP expression during gestation. On the other hand, the values of Bcrp −/−/WT ratio of K p,brain for genistein and dantrolene were 6.1 and 3.8, respectively, while the K p,fp ratios were all less than 2.0. These results indicate that the apparent impact of a single placental BCRP molecule on the restriction of drug distribution is much less than that of a single brain BCRP molecule, probably because the function of placental BCRP is attenuated by bypass transfer through the connexin26 gap junctions between adjacent syncytiotrophoblast layers. The present study also found that the expression amount of BCRP protein at the human placental barrier formed by the monolayer of syncytiotrophoblasts was lower than that in mice, but this species difference appears to be functionally compensated by the murine-specific bypass route through gap junctions, at least in part.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41445083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}