Delivery Barriers Research Articles

Focused Ultrasound-Mediated Intranasal Brain Drug Delivery Technique (FUSIN).

The blood-brain barrier (BBB) is the major barrier for brain drug delivery and limits the treatment options for central nervous system diseases. To circumvent the BBB, we introduced the focused ultrasound-mediated intranasal brain drug delivery (FUSIN) technique. FUSIN utilizes the nasal route for direct nose-to-brain drug administration, bypassing the BBB and minimizing systemic exposure. It also uses the transcranial application of ultrasound energy focused at a targeted brain region to induce microbubble cavitation, which enhances the transport of intranasally administered agents at the FUS-targeted brain location. FUSIN is unique in that it can achieve noninvasive and localized brain drug delivery with minimized systemic toxicity. The goal of this chapter is to provide a detailed protocol for FUSIN delivery to the mouse brain.

The influence of caregiver attitudes and socioeconomic group on formal and informal mental health service use among youth.

Young people can receive mental health care from many sources, from formal and informal sectors. Caregiver characteristics/experiences/beliefs may influence whether young people get help and the type of care or support used by their child. We investigate facilitators/barriers to receiving formal and/or informal care, particularly those related to the caregiver's profile. We interviewed 1,400 Brazilian primary caregivers of young people (aged 10-19), participants of a high-risk cohort. Caregivers reported on young people's formal/informal mental health care utilization, and associated barriers and facilitators to care. Data were also collected on youth mental health and its impact on everyday life; and caregiver characteristics-education, socioeconomics, ethnicity, mental health, and stigma. Logistic regression models were used to examine the relationship between caregiver and young people characteristics with formal/informal care utilization. Persistence and greater impact of youth mental health conditions were associated with a higher likelihood of care, more clearly for formal care. Caregiver characteristics, however, also played a key role in whether young people received any care: lower parental stigma was associated with greater formal service use, and lower socioeconomic class showed higher odds of informal care (mainly from religious leaders). This study highlights the key role of the caregivers as gatekeepers to child treatment access, particularly parental stigma influencing whether young people received any mental health care, even in a low resource setting. These results help to map barriers for treatment access and delivery for young people, aiming to improve intervention efforts and mental health support.

Transformable nanoparticles to bypass biological barriers in cancer treatment.

Nanomedicine based drug delivery platforms provide an interesting avenue to explore for the future of cancer treatment. Here we discuss the barriers for drug delivery in cancer therapeutics and how nanomaterials have been designed to bypass these blockades through stimuli responsive transformation in the most recent update. Nanomaterials that address the challenges of each step provide a promising solution for new cancer therapeutics.

Overcoming barriers in non-viral gene delivery for neurological applications.

Gene therapy for neurological disorders has attracted significant interest as a way to reverse or stop various disease pathologies. Typical gene therapies involving the central and peripheral nervous system make use of adeno-associated viral vectors whose questionable safety and limitations in manufacturing has given rise to extensive research into non-viral vectors. While early research studies have demonstrated limited efficacy with these non-viral vectors, investigation into various vector materials and functionalization methods has provided insight into ways to optimize these non-viral vectors to improve desired characteristics such as improved blood-brain barrier transcytosis, improved perfusion in brain region, enhanced cellular uptake and endosomal escape in neural cells, and nuclear transport of genetic material post- intracellular delivery. Using a combination of various strategies to enhance non-viral vectors, research groups have designed multi-functional vectors that have been successfully used in a variety of pre-clinical applications for the treatment of Parkinson's disease, brain cancers, and cellular reprogramming for neuron replacement. While more work is needed in the design of these multi-functional non-viral vectors for neural applications, much of the groundwork has been done and is reviewed here.

Investigating the Benefits and Barriers of Quality Assurance Management for Adequate Housing Delivery in Nigeria: An Empirical Overview

Abstract Purpose: The process of housing delivery all over the world is confronted by multiple barriers resulting in houses that are short of clients’ expectations in terms of quality and overall standards. The inability of the house builders (contractors) to deliver quality housing normally occurs due to non-conformance to quality assurance principles and non-adherence to the key quality indicators. An assessment of recent developments and actions in the building industry that might help mitigate the identified barriers has been made in this study. Hence, skilful application of quality assurance principles to overcome quality barriers in housing delivery is essential. Methodology: The study has employed quantitative methods of data collection. Closed-ended questionnaires have been prepared and administered to building contractors in Akure, Nigeria. The collected quantitative data have been analysed with the aid of SPSS software, version 27. The results have been accordingly reported to ascertain the level of commitment made by building contractors on ensuring quality in housing delivery in Akure. Findings: Findings have revealed that building contractors are well conversant and knowledgeable about the probable benefits of implementing quality assurance in the housing delivery process. There are, however, obvious challenges and serious barriers that are militating against effective implementation of quality assurance measures in the housing delivery process such as engaging unskilled labour force. Recommendation: The study recommends that a pre-assessment of the workforce be made to establish their level of knowledge and competencies on quality assurance management principles. Originality and value: Creation of “quality assurance consciousness” for the housing industry will result in quality housing delivery to the satisfaction of all end users and the general public.

Orally administrable polyphenol-based nanoparticles achieve anti-inflammation and antitumor treatment of colon diseases.

Colorectal cancer is the third most common malignancy that leads to significant mortality around the world. Chronic colonic inflammation could induce a protumor effect by the massive release of pro-inflammatory cytokines, facilitating migration, invasion, and metastasis of malignant cells in colorectal cancer. Therefore, developing a combination regimen of anti-inflammation and antitumor therapies is a promising strategy for the treatment of colorectal cancer. Here, we report that tannic acid-containing nanoparticles, formed by a turbulent-mixing technique, have exhibited uniform size, high stability, and pH-triggered drug release in the gastrointestinal tract, and could overcome intestinal mucosa for drug delivery in the colorectal region. As a drug carrier itself, with potent antioxidant and anti-inflammatory properties, tannic acid-containing nanoparticles showed great therapeutic effect in preventing the development of colitis-associated colorectal cancer (CAC) through oral administration. Furthermore, we used a therapeutic nanocarrier to deliver chemotherapeutic drugs for CAC treatment, generating lower systemic toxicity and superior antitumor performance through concurrent anti-inflammation and antitumor treatment. As a result, we confirmed that the drug carrier itself with therapeutic function could improve the overall therapeutic performance, and provided a safe and effective tannic acid-containing nanoplatform for the prevention and treatment of colon diseases.

The Impact of Work Environment on Nurses' Compassion: A Multicenter Cross-Sectional Study.

IntroductionCompassionate care is considered as the main part of the nurses’ identity and a core component of nursing care. One clinical environment where patients experience a lot of pain and nurses play a vital role in delivering care is the intensive care unit (ICU).ObjectiveConsidering the importance of compassionate care in intensive care units, this study aimed to assess the relationship between the work environment and nurses’ compassion in intensive care units.MethodsIn this cross-sectional survey, a total of 235 nurses were randomly selected from the intensive care units of four educational hospitals of Tabriz University of Medical Sciences from January to March 2021. Data were collected by demographic questionnaire, the Sussex-Oxford Compassion for Others Scale (SOCS-O) and the Practice Environment Scale of the Nursing Work Index (PES-NWI).ResultsThe results showed that there was a significant and inverse relationship between the patient per nurse ratio and the mean score of nurses’ compassion (P < .05). Moreover, Pearson correlation coefficient showed that the mean total score of the nursing work index had a significant positive relationship with the mean score of the compassion for others (r = 0.16, P = .016).ConclusionHealth care managers and leaders should pay more attention to the promotion of nurses’ working environments and they should remove the organizational barriers of compassionate care delivery.

Socio-professional Reintegration Services in the Era of the Covid-19 Pandemic in the Małopolska Region

Background: The research issues concern the most important aspects of socio-vocational reintegration and rehabilitation services (e.g. instruments of support, barriers of service delivery, effects of activities), cooperation in local communities and the scope of institutional support.&#x0D; Research objectives: The aim of this article is to present the most important implications of the coronavirus pandemic for socio-vocational reintegration services in reintegration units operating in the Małopolska Region.&#x0D; Research design and methods: The material constituting the basis for analysis is mainly the results of a survey conducted by the Regional Centre for Social Policy in Kraków in the framework of cyclical monitoring of the social economy sector in the Małopolska Region. 73 Reintegration Units participated in this part of the study out of 122 active ones in the Małopolska voivodeship in 2020.&#x0D; Results: The analysis makes it possible to conclude that the Covid-19 pandemic and related phenomena in the socio-economic sphere had a strong impact on the current functioning of reintegration units, reduced the scope of possible instruments for socio-occupational activation, which in turn had a negative impact on the results of support. The activities of the reintegration units, hampered by the pandemic, did not receive effective support from the public administration or local partners. The pandemic also limited the possibilities of cooperation between reintegration units in local communities.&#x0D; Conclusions: The long-term effects of which will probably be felt for an unspecified period of time, in order to improve the quality and effectiveness of socio-occupational reintegration services provided by reintegration units.

On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles

Lipid nanoparticles (LNPs) are a clinically mature technology for the delivery of genetic medicines but have limited therapeutic applications due to liver accumulation. Recently, our laboratory developed selective organ targeting (SORT) nanoparticles that expand the therapeutic applications of genetic medicines by enabling delivery of messenger RNA (mRNA) and gene editing systems to non-liver tissues. SORT nanoparticles include a supplemental SORT molecule whose chemical structure determines the LNP's tissue-specific activity. To understand how SORT nanoparticles surpass the delivery barrier of liver hepatocyte accumulation, we studied the mechanistic factors which define their organ-targeting properties. We discovered that the chemical nature of the added SORT molecule controlled biodistribution, global/apparent pKa, and serum protein interactions of SORT nanoparticles. Additionally, we provide evidence for an endogenous targeting mechanism whereby organ targeting occurs via 1) desorption of poly(ethylene glycol) lipids from the LNP surface, 2) binding of distinct proteins to the nanoparticle surface because of recognition of exposed SORT molecules, and 3) subsequent interactions between surface-bound proteins and cognate receptors highly expressed in specific tissues. These findings establish a crucial link between the molecular composition of SORT nanoparticles and their unique and precise organ-targeting properties and suggest that the recruitment of specific proteins to a nanoparticle's surface can enable drug delivery beyond the liver.

Advancing State and Local Home Modification Practice and Policy: Findings From Aging Network Surveys

Home modification (HM) can promote older adults’ functioning as their needs change, reduce fall risks, and support caregivers. A supportive home environment is increasingly important as homes become healthcare delivery sites for home and community-based services (HCBS). HM is funded and administered by disparate agencies, often hindering access to HM services for at-risk older adults who need them the most. The Aging Network (State Units on Aging (SUAs), Area Agencies on Aging (AAAs), and Title VI organizations serving Native American older adults) plays an important but not well understood role in HM. To address this lack of research, the USC Leonard Davis School of Gerontology, ADvancing States, and the National Association of Area Agencies on Aging in cooperation with Scripps Gerontology Center conducted three national surveys, with support from the Administration for Community Living: 1) directors of the 56 SUAs with an 89% response rate; 2) directors of the 618 AAAs with a 79% response rate; and 3) directors of 276 Title VI programs with an 84% response rate. Exemplary practices included HM advocacy through interagency coalitions; state and local plan priority setting; creative HM financing with housing, disability, and health care sectors, including partnerships with Medicaid agencies; and integration of HMs into state and local HCBS, including nursing home transition and caregiver support programs. Findings on the types of HM activities, service delivery barriers, funding sources, collaborations, and targeted populations will inform HM policy and practice for the Aging Network’s critical state and local agencies serving low-income older adults.

Dual-modified nanoparticles overcome sequential absorption barriers for oral insulin delivery

The efficacy of oral insulin drug delivery is seriously hampered by multiple gastrointestinal barriers, especially transepithelial barriers, including apical endocytosis, lysosomal degradation, cytosolic diffusion and basolateral exocytosis. In this study, a functional nanoparticle (PG-FAPEP) with dual-modification was constructed to sequentially address these important absorption obstacles for improved oral insulin delivery. The dual surface decorations folate and charge-convertible tripeptide endowed PG-FAPEP with the ability to target the apical and basolateral sides of enterocytes, respectively. After fast diffusion across the mucus layer, PG-FAPEP could be efficiently internalized into epithelial cells via a folate receptor-mediated pathway and subsequently became positively charged in acidic lysosomes due to the surface tripeptide, triggering the proton sponge effect to escape lysosomes. When entering the cytosolic medium, PG-FAPEP was converted to neutral charge again, attenuating intracellular adhesion, and gained improved motility toward the basolateral side. Finally, the tripeptide helped PG-FAPEP recognize the proton-coupled oligopeptide transporter (PHT1) in the basolateral membrane, boosting intact exocytosis across intestinal epithelial cells. The in vivo studies further verified that PG-FAPEP could traverse the intestinal epithelium by folate receptor-mediated endocytosis, lysosomal escape, and PHT1-mediated exocytosis, exhibiting a high oral insulin bioavailability of 14.3% and a prolonged hypoglycemic effect. This formulation addresses multiple absorption barriers on demand with a simple dual-modification strategy. Therefore, these features allow PG-FAPEP to unleash the potential of oral macromolecule delivery.

Novel Fluorinated Spermine and Small Molecule PEI to Deliver Anti-PD-L1 and Anti-VEGF siRNA for Highly Efficient Tumor Therapy.

Small interfering RNA (siRNA) can specifically silence disease gene expression. This project investigated the overexpression of programmed death receptor ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) on the surface of tumor cells. However, the main obstacle to the development of gene therapy drugs is the lack of an efficient delivery vector, which should be able to overcome multiple delivery barriers and protect siRNA to enter the target cells. Therefore, a novel fluorine-modified endogenous molecular carrier TFSPEI was constructed by linking fluorinated groups with hydrophobic and hydrophilic characteristics on the surface of PEI and spermine. The results showed that lower toxicity, higher endocytosis, and silencing efficiency were achieved. We found that the inhibition of VEGF targets can indirectly activate the immune response to promote the tumor-killing and invasion effects of T cells. The combined delivery of anti-VEGF siRNA and anti-PD-L1 siRNA could inhibit the expression of corresponding proteins, restore the anti-tumor function of T cells and inhibit the growth of neovascularization, and obtained significant anti-tumor effects. Therefore, this safe and efficient fluorinated spermine and small molecule PEI-based anti-PD-L1 and anti-VEGF siRNA delivery system is expected to provide a new strategy for gene therapy of tumors.

Disrupting stromal barriers to enhance photothermal-chemo therapy using a halofuginone-loaded Janus mesoporous nanoplatform

Dense tumor stroma is the physiological barrier in drug delivery that prevents anticancer drugs from entering the tumor, thereby seriously limiting the drugs' therapeutic effect. In this study, a Janus nanoplatform consisting of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) and anti-stroma drug halofuginone (HF) (denoted as JPMO-Pt-HF), was developed to deplete the tumor stroma and synergistically treat breast cancer in BALB/c mice. The prepared JPMO-Pt had a uniform size of 245 nm, a good dispersion, an excellent in vitro and in vivo biocompatibility, and a high loading capacity for HF (up to 50 μg/mg). The antitumor experiments showed that the survival rate of 4 T1 cells exhibited an obvious downward trend when the cells were incubated with the JPMO-Pt-HF and irradiated with 808 nm laser. Moreover, the cell survival rate was only about 10% at 48 h when the HF concentration was 2.0 μg/mL. Notably, JPMO-Pt-HF under irradiation had an excellent synergistic therapeutic effect on tumor cells. In vivo antitumor experiment further showed that the JPMO-Pt-HF, in combination with laser irradiation, could minimize tumor growth, showing significantly better effects than those observed for the case of monotherapy involving photothermal therapy (PTT) (152 vs. 670 mm3, p < 0.0001) and HF (152 vs. 419 mm3, p = 0.0208). In addition, immunohistochemistry of tumor tissues indicated that JPMO-Pt-HF obviously reduced the relative collagen and α-smooth muscle actin (α-SMA) area fraction. Taken together, this research designs a new platform that not only possesses the ability to degrade the tumor matrix but also combines PTT and chemotherapeutic effects, and holds promise for effective tumor treatment.

Modulation of the Blood-Brain Barrier for Drug Delivery to Brain.

The blood–brain barrier (BBB) precisely controls brain microenvironment and neural activity by regulating substance transport into and out of the brain. However, it severely hinders drug entry into the brain, and the efficiency of various systemic therapies against brain diseases. Modulation of the BBB via opening tight junctions, inhibiting active efflux and/or enhancing transcytosis, possesses the potential to increase BBB permeability and improve intracranial drug concentrations and systemic therapeutic efficiency. Various strategies of BBB modulation have been reported and investigated preclinically and/or clinically. This review describes conventional and emerging BBB modulation strategies and related mechanisms, and safety issues according to BBB structures and functions, to try to give more promising directions for designing more reasonable preclinical and clinical studies.

Engineered Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as New Generations of Blood-Brain Barrier Transmitters.

The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.

Pharmacological Activation of cGAS for Cancer Immunotherapy.

When compartmentally mislocalized within cells, nucleic acids can be exceptionally immunostimulatory and can even trigger the immune-mediated elimination of cancer. Specifically, the accumulation of double-stranded DNA in the cytosol can efficiently promote antitumor immunity by activating the cGAMP synthase (cGAS) / stimulator of interferon genes (STING) cellular signaling pathway. Targeting this cytosolic DNA sensing pathway with interferon stimulatory DNA (ISD) is therefore an attractive immunotherapeutic strategy for the treatment of cancer. However, the therapeutic activity of ISD is limited by several drug delivery barriers, including susceptibility to deoxyribonuclease degradation, poor cellular uptake, and inefficient cytosolic delivery. Here, we describe the development of a nucleic acid immunotherapeutic, NanoISD, which overcomes critical delivery barriers that limit the activity of ISD and thereby promotes antitumor immunity through the pharmacological activation of cGAS at the forefront of the STING pathway. NanoISD is a nanoparticle formulation that has been engineered to confer deoxyribonuclease resistance, enhance cellular uptake, and promote endosomal escape of ISD into the cytosol, resulting in potent activation of the STING pathway via cGAS. NanoISD mediates the local production of proinflammatory cytokines via STING signaling. Accordingly, the intratumoral administration of NanoISD induces the infiltration of natural killer cells and T lymphocytes into murine tumors. The therapeutic efficacy of NanoISD is demonstrated in preclinical tumor models by attenuated tumor growth, prolonged survival, and an improved response to immune checkpoint blockade therapy.

Overcoming barriers of retinal care delivery during a pandemic—attitudes and drivers for the implementation of digital health: a global expert survey

Background/AimsThe SARS-CoV-2 pandemic has imposed barriers to retinal care delivery worldwide. In this context, retinal services are exploring novel ways to ensure access to healthcare.MethodsWe conducted a worldwide survey among...

Brief mindfulness-oriented interventions (MOIs) to improve psychiatric symptoms in a psychiatric inpatient unit: a randomized controlled feasibility trial

ABSTRACT Background Mindfulness-based interventions are effective in treating numerous psychiatric symptoms, but data about brief mindfulness-oriented intervention (MOI) use with psychiatric inpatients are limited. We investigated whether a brief MOI was feasible and effective in reducing psychosis and other symptoms in a psychiatric inpatient unit. Methods In an assessor-blinded feasibility randomized-controlled trial, adult psychiatric inpatients were randomized to the intervention or control group. Feasibility outcomes included enrollment rate, retention rate and intervention-completion rate. The quantitative outcome was the impact on symptom reduction (mean and % difference in Brief Psychiatric Rating Scale (BPRS) between baseline and 7-day follow-up scores). Exploratory outcomes included improvement in quality of sleep, mindfulness and quality of life. Qualitative intervention feedback was obtained from therapists and participants. Results Feasibility outcomes were 39.2% participant enrollment, 85% study completion and 81.8% intervention completion. No symptom outcomes significantly differed. There were no significant differences in exploratory outcomes. Interventionists reported system-level barriers in treatment delivery; patients subjectively reported enjoying the intervention. Discussion The MOI is feasible in the inpatient psychiatric setting. There were no significant effects on psychiatric symptoms during the follow-up period, but no adverse effects were reported. Therapeutic effects could be further investigated in longer-term interventions and larger confirmatory RCTs.

Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye.

Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy to apply by patients. However, conventional drug formulations are usually characterized by short retention time in the tear film, insufficient contact with epithelium, fast elimination, and difficulties in overcoming ocular tissue barriers. Not more than 5% of the total drug dose administered in eye drops reaches the interior ocular tissues. To overcome the ocular drug delivery barriers and improve drug bioavailability, various conventional and novel drug delivery systems have been developed. Among these, nanosize carriers are the most attractive. The review is focused on the different drug carriers, such as synthetic and natural polymers, as well as inorganic carriers, with special attention to nanoparticles and nanomicelles. Studies in vitro and in vivo have demonstrated that new formulations could help to improve the bioavailability of the drugs, provide sustained drug release, enhance and prolong their therapeutic action. Promising results were obtained with drug-loaded nanoparticles included in in situ gel.

Recent Advances in the Noninvasive Delivery of mRNA.

Over the past two decades, research on mRNA-based therapies has exploded, mainly because of the inherent advantages of mRNA, including a low integration probability, transient expression, and simple and rapid in vitro transcription production approaches. In addition, thanks to improved stability and reduced immunogenicity by advanced strategies, the application of mRNA has expanded from protein replacement therapy to vaccination, gene editing and other fields, showing great promise for clinical application. Recently, with the successive launch of two mRNA-based COVID-19 vaccines, mRNA technology has attracted an enormous amount of attention from scientific researchers as well as pharmaceutical companies. Because of the large molecular weight, hydrophilicity, and highly negative charge densities of mRNA, it is difficult to overcome the intracellular delivery barriers. Therefore, various delivery vehicles have been developed to achieve more effective mRNA delivery. In general, conventional mRNA administration methods are based on injection strategies, including intravenous, intramuscular, intradermal, and subcutaneous injections. Although these routes circumvent the absorption barriers to some extent, they bring about injection-related concerns such as safety issues, pain, low compliance, and difficulty in repeated dosing, increasing the need to explore alternative strategies for noninvasive delivery. The ideal noninvasive delivery systems are featured with easy to use, low risks of infection, and good patient compliance. At the same time, they allow patients to self-administer, reducing reliance on professional healthcare workers and interference with bodily functions and daily life. In particular, the noninvasive mucosal delivery of mRNA vaccines can induce mucosal immune responses, which are important for resisting pathogens infected through mucosal routes.Because of the potential clinical benefits mentioned above, we detailed the existing strategies for the noninvasive delivery of mRNA in this review, including delivery via the nasal, pulmonary, vaginal, and transdermal routes. First, we discussed the unique strengths and biological hindrances of each route on the basis of physiology. Next, we comprehensively summarized the research progress reported so far and analyzed the technologies and delivery vehicles used, hoping to provide some references for further explorations. Among these noninvasive routes, nasal and pulmonary delivery are the earliest and most intensively studied areas, mostly owing to their favorable physiological structures: the nasal or pulmonary mucosa is easily accessible, highly permeable and highly vascularized. In contrast, the development of vaginal mRNA delivery is relatively less reported, and the current research mainly focused on some local applications. In addition, microneedles have also been investigated to overcome skin barriers for mRNA delivery in recent years, making microneedle-based delivery an emerging alternative pathway. In summary, a variety of mRNA formulations and delivery strategies have been developed for noninvasive mRNA delivery, skillfully combining appropriate vehicles or physical technologies to enhance effectiveness. We surmise that continuous advances and technological innovations in the development of mRNA noninvasive delivery will accelerate the translation from experimental research to clinical application.