Abstract:The skin is the largest and most accessible organ in the human body and, as such, it appears as the most convenient portal for drug delivery. However, the skin is also a formidable barrier which, while protecting us from physical, chemical, and immunological agents, requires appropriate technology for effective delivery. Today, the most effective administration method for large, lipophobic, and polar molecules continues to be hypodermic injection, which is associated with pain, needle phobia, and stick injury.… Show more
“…Despite the attractive advantages of cutaneous vaccination over prevailing immunization routes, the skin has been an underutilized organ for clinical immunization largely due to the lack of effective drug delivery systems that can enable safe, reproducible, and patient-friendly deployment of antigens to skin microenvironments [64,[68][69][70][71]. Palpably, the stratum corneum, the outermost layer of the skin (Figure 1), consists of dead keratinocytes (corneocytes) and constitutes a formidable physical barrier to delivery of vaccine components to immunologically rich skin layers (viable epidermis and dermis, Figure 1), thereby necessitating sophisticated skin-targeted drug delivery strategies for effective intracutaneous immunization [72][73][74]. Topical drug delivery is an appealing method for patients due to its simplicity and non-invasiveness; however, topical administration of antigenic compounds and biological adjuvants, which are relatively complex biomolecules, is hampered by the formidable barrier function of the superficial cutaneous layers, which substantially reduces the bioavailability of vaccines, and in turn, the efficacy of immunization [75][76][77].…”
Section: Intracutaneous Drug Delivery Strategiesmentioning
Introduction: Infectious pathogens are global disrupters. Progress in biomedical science and technology has expanded the public health arsenal against infectious diseases. Specifically, vaccination has reduced the burden of infectious pathogens. Engineering systemic immunity by harnessing the cutaneous immune network has been particularly attractive since the skin is an easily accessible immuneresponsive organ. Recent advances in skin-targeted drug delivery strategies have enabled safe, patientfriendly, and controlled deployment of vaccines to cutaneous microenvironments for inducing longlived pathogen-specific immunity to mitigate infectious diseases, including COVID-19.Areas covered: This review briefly discusses the basics of cutaneous immunomodulation and provides a concise overview of emerging skin-targeted drug delivery systems that enable safe, minimally invasive, and effective intracutaneous administration of vaccines for engineering systemic immune responses to combat infectious diseases. Expert opinion: In-situ engineering of the cutaneous microenvironment using emerging skin-targeted vaccine delivery systems offers remarkable potential to develop diverse immunization strategies against pathogens. Mechanistic studies with standard correlates of vaccine efficacy will be important to compare innovative intracutaneous drug delivery strategies to each other and to existing clinical approaches. Cost-benefit analyses will be necessary for developing effective commercialization strategies. Significant involvement of industry and/or government will be imperative for successfully bringing novel skin-targeted vaccine delivery methods to market for their widespread use.
“…Despite the attractive advantages of cutaneous vaccination over prevailing immunization routes, the skin has been an underutilized organ for clinical immunization largely due to the lack of effective drug delivery systems that can enable safe, reproducible, and patient-friendly deployment of antigens to skin microenvironments [64,[68][69][70][71]. Palpably, the stratum corneum, the outermost layer of the skin (Figure 1), consists of dead keratinocytes (corneocytes) and constitutes a formidable physical barrier to delivery of vaccine components to immunologically rich skin layers (viable epidermis and dermis, Figure 1), thereby necessitating sophisticated skin-targeted drug delivery strategies for effective intracutaneous immunization [72][73][74]. Topical drug delivery is an appealing method for patients due to its simplicity and non-invasiveness; however, topical administration of antigenic compounds and biological adjuvants, which are relatively complex biomolecules, is hampered by the formidable barrier function of the superficial cutaneous layers, which substantially reduces the bioavailability of vaccines, and in turn, the efficacy of immunization [75][76][77].…”
Section: Intracutaneous Drug Delivery Strategiesmentioning
Introduction: Infectious pathogens are global disrupters. Progress in biomedical science and technology has expanded the public health arsenal against infectious diseases. Specifically, vaccination has reduced the burden of infectious pathogens. Engineering systemic immunity by harnessing the cutaneous immune network has been particularly attractive since the skin is an easily accessible immuneresponsive organ. Recent advances in skin-targeted drug delivery strategies have enabled safe, patientfriendly, and controlled deployment of vaccines to cutaneous microenvironments for inducing longlived pathogen-specific immunity to mitigate infectious diseases, including COVID-19.Areas covered: This review briefly discusses the basics of cutaneous immunomodulation and provides a concise overview of emerging skin-targeted drug delivery systems that enable safe, minimally invasive, and effective intracutaneous administration of vaccines for engineering systemic immune responses to combat infectious diseases. Expert opinion: In-situ engineering of the cutaneous microenvironment using emerging skin-targeted vaccine delivery systems offers remarkable potential to develop diverse immunization strategies against pathogens. Mechanistic studies with standard correlates of vaccine efficacy will be important to compare innovative intracutaneous drug delivery strategies to each other and to existing clinical approaches. Cost-benefit analyses will be necessary for developing effective commercialization strategies. Significant involvement of industry and/or government will be imperative for successfully bringing novel skin-targeted vaccine delivery methods to market for their widespread use.
“…On the basis of the previous studies, it can be seen that the functional design of MN drug delivery systems using nano-engineering technology could make it possible to realize intelligent control of drug release amount, release kinetics, or stimuli-responsive delivery. The main advantage of nanomaterials is that they can be designed for specific functions, and are responsive to specific microenvironments [ 5 ]. There are special microenvironments and landmark substances at the lesion site that could be extensively harnessed for the design of functional nanomaterials incorporating MNs for different diseases therapy.…”
Section: Outlook: Nanotechnology Potentiates Mns In Biomedicinementioning
confidence: 99%
“…The skin is the largest organ, and is a strong biological barrier, preventing infectious diseases and harmful substances from entering the body. However, the skin is also a major barrier to the effective delivery of drugs to lesions via percutaneous administration, while meanwhile also being susceptible to pain [ 5 ]. The skin consists of three morphologically distinct layers: the cuticle, the living epidermis, and the dermis [ 6 ].…”
For decades, scientists have been doing a lot of research and exploration to find effective long-term analgesic and/or disease-modifying treatments. Microneedles (MNs) are a simple, effective, and painless transdermal drug delivery technology that has emerged in recent years, and exhibits great promise for realizing intelligent drug delivery. With the development of materials science and fabrication technology, the MN transdermal drug delivery technology has been applied and popularized in more and more fields, including chronic illnesses such as arthritis or diabetes, cancer, dermatocosmetology, family planning, and epidemic disease prevention, and has made fruitful achievements. This paper mainly reviews the latest research status of MNs and their fabrication methodology, and summarizes the application of MNs in the treatment of various diseases, as well as the potential to use nanotechnology to develop more intelligent MNs-based drug delivery systems.
“…[ 19 ] Other applications include the delivery of pharmaceuticals for the treatment of cancer, skin conditions, bacterial infections, and osteoporosis. [ 20 ] Microneedles have also been applied for local anesthesia, pain management, and contraceptive purposes. More recently, microneedles have been used to sample skin fluids for diagnosis and health monitoring.…”
Engineered nano–bio interfaces–driven by vertical micro/nanoneedles, nanoparticles, organ‐on‐chip devices, and a diversity of nanosubstrates for mass spectroscopy imaging–are spurring scientific and technological progress, from fundamental to transnational biomedical research. Each class has its own characteristic features, which is critical for their translational uptake, but they broadly share the same range of functionality and applicability at the forefront of modern research and medicine. The review provides insights into unique attributes of microneedle technology and its ability for efficient transdermal transport of therapeutic compounds. The uses of nanoneedle technology in precise manipulation of increasingly complex cellular processes at the cell–material interface and their potential for major improvements for many fundamental research applications and ex vivo cell‐based therapies are highlighted. A snapshot in the use of food and drug administration (FDA)‐approved nanoparticle therapeutics and their applications in nanomedicine is provided. The achievements in organ‐on‐chip technology, particularly at the preclinical stage, and its potential to efficiently screen diverse types of therapeutics are covered. The final section is dedicated to the use of nanomaterial‐enhanced mass spectrometry in drug discovery and imaging. Overall, this review aims to highlight those main rules in the design of bio–nano interfaces that have successfully achieved translation into the market.
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