Poly­d,l­lactic acid­enhanced atrophic scar treatment via transdermal microjet drug delivery in Asians.

BACKGROUND: Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods. OBJECTIVE: This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars. METHODS: Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores. RESULTS: Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period. CONCLUSION: Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes.

Efficacy of articaine anesthesia with needle-free/Comfort-in method and conventional needle injection in dental patients with irreversible pulpitis: a randomized clinical trial.

OBJECTIVE: To assess the anesthetic efficacy of articaine with the needle-free/Comfort-in™ method compared to the conventional needle method. To assess pain during anesthesia application, onset of anesthesia and patient`s self-reported quality of life-related to oral health after the dental emergency appointment. MATERIALS AND METHODS: This parallel, randomized clinical trial was conducted by a single operator/dentist in the state of Maranhao, northeast of Brazil. Included participants were adult dental patients with one molar (maxillary) or premolar (maxillary or mandibular) tooth diagnosed with symptomatic irreversible pulpitis. The primary outcome was the anesthetic efficacy, measured using a combination of electrical and cold pulp tests (cold + EPT) and the Numerical Rating Scale (NRS). Secondary outcomes were pain during anesthesia application, onset of anesthesia, and patient`s quality-of-life (measured with the OHIP-14). RESULTS: 62 patients were randomized in the anesthesia needle-free group and Comfort-in group (34.26 ± 10.786 × 33.29 ± 8.399 years old, respectively). The group of patients in the Comfort-in group had 71.0% success. Patients from the Comfort-in group reported statistically lower pain during the anesthesia application than patients from the conventional group (2.13 ± 2.172 × 6.03 ± 3.146 NRS scores, respectively) as well as immediately after the anesthetic procedure. Patients self-reported negative impact in quality of life was similar between groups before (p > 0.05) and after (p > 0.05) the dental emergency. CONCLUSIONS: Comfort-in™ had similar efficacy to the conventional needle method. CLINICAL RELEVANCE: This trial showed that it is possible to anesthetize patients with tooth pulpits without using needles to provide comfort mainly to anxious patients.

Effect of a needle-free system versus traditional anesthesia on pain perception during palatal injections in children.

BACKGROUND: Needle-free injection systems can contribute to the prevention of needle-related pain during palatal infiltration anesthesia (PIA) in children. Research on this topic in children is required. AIM: The purpose of this clinical study was to evaluate the effectiveness and patient preference of a needle-free system versus traditional anesthesia (TA) on pain perception during PIA in children. DESIGN: The study was designed as a randomized, controlled crossover clinical study with 48 children aged 6-12 years requiring dental treatment with PIA in bilateral maxillary primary molars. TA was applied on one side and the Comfort-in™ injection system (CIS) on the other side in two separate sessions. Then, patient preference was recorded. The pain perception during PIA was evaluated using the Wong-Baker FACES Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. The data were analyzed for statistical significance (p < .05). RESULTS: There were statistically significant differences between the TA and the CIS according to the PRS and FLACC Scale scores. On both scales, significantly higher pain ratings were observed in the TA group during PIA (p < .001). There was a statistically significant difference in terms of patient preference (p < .001). Although 77.1% (n = 37) of the children preferred the CIS, 22.9% (n = 11) preferred the TA. Moreover, patient preference for the CIS was significantly higher in older children (p < .01). CONCLUSIONS: The application of a needle-free system during PIA ensured a decrease in pain perception in children.

Comparative evaluation of pain perception with a new needle-free system and dental needle method in children: a randomized clinical trial.

BACKGROUND: Pain control during dental procedures is one of the most important topics related to behavior management in children. This study aims to compare the pain perception associated with a needle-free system (Comfort-In™) and the dental needle method during filling and pulpotomy treatments in children. METHODS: The study included teeth that required treatment (pulpotomy or filling treatment) in 56 patients aged 4 to 11 years with no systemic problems or history of allergy. Patients were randomly divided into the needle-free system group (filling treatment, n = 13; pulpotomy, n = 15) and dental needle method group (filling treatment, n = 14; pulpotomy, n = 14). For pulpotomy and filling treatment performed with 0.3 mL anesthesia, the active ingredient of which is 2% lidocaine and 1/80000 epinephrine. The patients' behavior before the procedure was evaluated by a pediatric dentist using the Frankl Behavior Scale. The pain intensity was assessed Immediately after injection (induction), during treatment (treatment), and at the end of the treatment (post treatment) by the Wong-Baker Faces Pain Scale. RESULTS: The median (IQR-InterQuartile Range) induction pain value was 6[3-8] and 2[0-4] in dental needle method and needle-free system respectively, p < 0.001). In filling and pulpotomy treatment group, no difference between the needle and needle-free group for treatment and post-treatment pain values. CONCLUSIONS: For pulpotomy and filling treatment, needle-free system performed with 0.3 mL anesthesia was found as effective as infiltrative anesthesia with a dental needle method. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04653974 . Registered 4 December 2020 - Retrospectively registered.

Needle-free jet injection of intact phospholipid vesicles across the skin: a feasibility study.

Needle-free liquid jet injectors are devices developed for the delivery of pharmaceutical solutions through the skin. In this paper, we investigated for the first time the ability of these devices to deliver intact lipid vesicles. Diclofenac sodium loaded phospholipid vesicles of two types, namely liposomes and transfersomes, were prepared and fully characterized. The lipid vesicles were delivered through a skin specimen using a jet injector and the collected samples were analyzed to assess vesicle structural integrity, drug retention and release kinetics after the injection. In this regard, data concerning size, size distribution, surface charge of vesicles and bilayer integrity and thickness, before and after the injections, were measured by dynamic light scattering experiments, cryo-electron microscopy, and X-ray scattering techniques. Finally, the effect of vesicle fast jet injection through the skin on drug release kinetics was checked by in vitro experiments. The retention of the morphological, physico-chemical, and technological features after injection, proved the integrity of vesicles after skin crossing as a high-speed liquid jet. The delivery of undamaged vesicular carriers beneath the skin is of utmost importance to create a controlled release drug depot in the hypoderm, which may be beneficial for several localized therapies. Overall results reported in this paper may broaden the range of application of liquid jet injectors to lipid vesicle based formulations thus combining beneficial performance of painless devices with those of liposomal drug delivery systems.

Investigating skin penetration depth and shape following needle-free injection at different pressures: A cadaveric study.

BACKGROUND AND OBJECTIVES: The effectiveness of needle-free injection devices in neocollagenesis for treating extended skin planes is an area of active research. It is anticipated that needle-free injection systems will not only be used to inject vaccines or insulin, but will also greatly aid skin rejuvenation when used to inject aesthetic materials such as hyaluronic acid, botulinum toxin, and placental extracts. There has not been any specific research to date examining how materials penetrate the skin when a needle-free injection device is used. In this study, we investigated how material infiltrates the skin when it is injected into a cadaver using a needle-free device. STUDY DESIGN/MATERIALS AND METHODS: Using a needle-free injector (INNOJECTOR™; Amore Pacific, Seoul, Korea), 0.2 ml of 5% methylene blue (MB) or latex was injected into cheeks of human cadavers. The device has a nozzle diameter of 100 µm and produces a jet with velocity of 180 m/s. This jet penetrates the skin and delivers medicine intradermally via liquid propelled by compressed gasses. Materials were injected at pressures of 6 or 8.5 bars, and the injection areas were excised after the procedure. The excised areas were observed visually and with a phototrichogram to investigate the size, infiltration depth, and shape of the hole created on the skin. A small part of the area that was excised was magnified and stained with H&E (×40) for histological examination. RESULTS: We characterized the shape, size, and depth of skin infiltration following injection of 5% MB or latex into cadaver cheeks using a needle-free injection device at various pressure settings. Under visual inspection, the injection at 6 bars created semi-circle-shaped hole that penetrated half the depth of the excised tissue, while injection at 8.5 bars created a cylinder-shaped hole that spanned the entire depth of the excised tissue. More specific measurements were collected using phototrichogram imaging. The shape of the injection entry point was consistently spherical regardless of the amount of pressure used. When injecting 5% MB at 6 bars, the depth of infiltration reached 2.323 mm, while that at 8.5 bars reached 8.906 mm. The area of the hole created by the 5% MB injection was 0.797 mm(2) at 6 bars and 0.242 mm(2) at 8.5 bars. Latex injections reached a depth of 3.480 mm at 6 bars and 7.558 mm at 8.5 bars, and the areas were measured at 1.043 mm(2) (6 bars) and 0.355 mm(2) (8.5 bars). Histological examination showed that the injection penetrated as deep as the superficial musculoaponeurotic system at 6 bars and the masseter muscle at 8.5 bars. CONCLUSION: When injecting material into the skin using a pneumatic needle-free injector, higher-pressure injections result in a hole with smaller area than lower-pressure injections. The depth and shape of skin penetration vary according to the amount of pressure applied. For materials of low density and viscosity, there is a greater difference in penetration depth according to the degree of pressure. Lasers Surg. Med. 48:624-628, 2016. © 2016 Wiley Periodicals, Inc.

Intradermal Inoculation of Inactivated Foot-and-Mouth Disease Vaccine Induced Effective Immune Responses Comparable to Conventional Intramuscular Injection in Pigs.

All pigs in the Republic of Korea are given the foot-and-mouth disease virus (FMDV) vaccine intramuscularly (IM) as part of the country's vaccination policy. However, the IM administration of the FMDV vaccine to pig results in residual vaccine components in the muscle and undesirable changes in muscle and soft tissues, causing economic losses in swine production. In this study, we evaluated whether intradermal (ID) vaccination could be proposed as an alternative to IM administration. ID vaccination (0.2 mL on each side of the neck muscle) and IM vaccination (2 mL on each side of the neck muscle) were performed twice, separated by 14 days, using a commercial FMD vaccine in specific-pathogen-free pigs. We observed growth performance, gross and microscopic lesions at the inoculation site, FMDV-specific antibodies, and neutralizing antibodies for 35 days after vaccination. Side effects on the skin grossly appeared following ID administration, but most were reduced within two weeks. All ID-vaccinated pigs showed inflammatory lesions limited to the dermis, but IM-vaccinated pigs had abnormal undesirable changes and pus in the muscle. ID-vaccinated pigs performed comparably to IM-vaccinated pigs in terms of growth, FMD virus-specific antibodies, protection capability against FMDV, and T-cell induction. This study demonstrated that the ID inoculation of the inactivated FMD vaccine induced immune responses comparable to an IM injection at 1/10 of the inoculation dose and that the inoculation lesion was limited to the dermis, effectively protecting against the formation of abnormal undesirable changes in muscle and soft tissues.

Comparative Evaluation of the Anesthetic Efficacy of Needle-Free Anesthesia and Conventional Anesthesia in Patients With Symptomatic Irreversible Pulpitis: A Randomized Clinical Trial.

Introduction Pain is the primary reason for which most of the patients seek endodontic treatment. Local anesthesia is considered to be the most important step in the procedure to reduce the pain. However, the majority of the patients do not cooperate due to the fear of syringe anesthesia. The aim of this clinical trial was to compare the anesthetic efficacy of needle-free anesthesia and conventional anesthesia in patients with symptomatic irreversible pulpitis undergoing root canal therapy. Materials and methods A total of 54 patients were enrolled in the study, and the treatment was administered by a single operator. The initial assessment of vitality included cold testing, heat testing, and electric pulp testing. Preoperative pain was assessed using the Visual Analog Scale (VAS) before the administration of anesthesia. Local anesthesia was administered according to the group assigned: Group 1 (conventional anesthesia) and Group 2 (needle-free anesthesia). The pain was assessed during the administration of anesthesia. Following the administration of anesthesia, the vitality of the tooth was evaluated using cold testing, heat testing, and electric pulp testing. Subsequently, the tooth was isolated with a rubber dam, and the access cavity was prepared. The pain was assessed during access cavity preparation and during the first file insertion. Working length was determined using an apex locator (Root ZX Mini, J Morita, Saitama, Japan) and was confirmed using intraoral periapical radiographs. Later on, further treatment was carried out. Results A total of 54 participants were included in this clinical trial. There was no significant difference in mean age distribution between the two groups (p=0.852). Considering the frequency distribution of gender, there was no significant difference; however, Group 1 had more female participants (59.3%) compared to Group 2 (33.3%). There was a significant reduction in the mean pain score in Group 2 compared to Group 1 during the delivery of anesthetic agents (p=0.000). Conclusion Needle-free anesthesia proves to be equally effective as the conventional syringe system in patients experiencing symptomatic irreversible pulpitis undergoing root canal treatment. However, it is noteworthy that patients exhibited greater comfort levels with needle-free anesthesia systems specifically during the administration of the anesthetic solution.

Liposome-based vaccines for minimally or noninvasive administration: an update on current advancements.

INTRODUCTION: Vaccination requires innovation to provide effective protection. Traditional vaccines have several drawbacks, which can be overcome with advanced technologies and different administration routes. Over the past 10 years, a significant amount of research has focussed on the delivery of antigens into liposomes due to their dual role as antigen-carrying systems and vaccine adjuvants able to increase the immunogenicity of the carried antigen. AREAS COVERED: This review encompasses the progress made over the last 10 years with liposome-based vaccines designed for minimally or noninvasive administration, filling the gaps in previous reviews and providing insights on composition, administration routes, results achieved, and Technology Readiness Level of the most recent formulations. EXPERT OPINION: Liposome-based vaccines administered through minimally or noninvasive routes are expected to improve efficacy and complacency of vaccination programs. However, the translation from lab-scale production to large-scale production and collaborations with hospitals, research centers, and companies are needed to allow new products to enter the market and improve the vaccination programs in the future.

Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery.

Transcutaneous immunization (TCI) via needle-free and non-invasive drug delivery systems is a promising approach for overcoming the current limitations of conventional parenteral vaccination methods. The targeted access to professional antigen-presenting cell (APC) populations within the skin, such as Langerhans cells (LCs), various dermal dendritic cells (dDCs), macrophages, and others makes the skin an ideal vaccination site to specifically shape immune responses as required. The stratum corneum (SC) of the skin is the main penetration barrier that needs to be overcome by the vaccine components in a coordinated way to achieve optimal access to dermal APC populations that induce priming of T-cell or B-cell responses for protective immunity. While there are numerous approaches to penetrating the SC, such as electroporation, sono- or iontophoresis, barrier and ablative methods, jet and powder injectors, and microneedle-mediated transport, we will focus this review on the recent progress made in particle-based systems for TCI. This particular approach delivers vaccine antigens together with adjuvants to perifollicular APCs by diffusion and deposition in hair follicles. Different delivery systems including nanoparticles and lipid-based systems, for example, solid nano-emulsions, and their impact on immune cells and generation of a memory effect are discussed. Moreover, challenges for TCI are addressed, including timely and targeted delivery of antigens and adjuvants to APCs within the skin as well as a deeper understanding of the ill-defined mechanisms leading to the induction of effective memory responses.

Proof of Concept for Prevention of Natural Colonization by Oral Needle-Free Administration of a Microparticle Vaccine.

There has been substantial interest in the development of needle-free vaccine administration that has led to a variety of approaches for delivery through the skin for induction of a systemic immune response. The mucosal administration of vaccines has inherently been needle-free, but the simple application of vaccines on the mucosal surface by itself does not lead to mucosal immunity. Since many important bacterial infections develop after initial colonization of the upper respiratory tract of the host, prevention of colonization could not only prevent infection but also eliminate the reservoir of pathogens that reside exclusively in that ecologic niche. This study was designed to provide proof of concept for a needle-free immunization approach that would reduce or eliminate colonization and prevent infection. In order to accomplish this a microparticle vaccine preparation was delivered just below the oral mucosal epithelial cell layer where it would lead to a robust immune response. A vaccine antigen (mutant transferrin binding protein B) shown to be capable of preventing infection in pigs was incorporated into a polyphosphazene microparticle preparation and delivered by a needle-free device to the oral sub-epithelial space of pigs. This vaccination regimen not only provided complete protection from infection after intranasal challenge by Glaesserella parasuis but also eliminated natural colonization by this bacterium. Notably, the complete prevention of natural colonization was dependent upon delivery of the microparticle preparation below the epithelial layer in the oral mucosa as intradermal or intramuscular delivery was not as effective at preventing natural colonization. This study also demonstrated that a primary immunization in the presence of maternal antibody limited the resulting antibody response but a robust antibody response after the second immunization indicated that maternal antibody did not prevent induction of B-cell memory.

Gadgets and Armamentarium of Maxillofacial Surgeons during Coronavirus Pandemic.

INTRODUCTION: We all know about the grave situation caused by the novel coronavirus in recent times. Although the maxillofacial surgeons are not at forefront of dealing with the coronavirus directly, they are at increased risk due to their working area on face, mouth, and oral cavity. There is an urgent need to upgrade the already set guidelines and follow them stringently. Any procedure done within the oral cavity is a high-risk procedure and this upgradation is necessary because present means are insufficient to prevent infection from this deadly virus. This article aims to review and discuss all the new gadgets and armamentarium required to deal with patients during and post coronavirus pandemic. MATERIALS AND METHODS: The authors performed a thorough literature search on various armamentarium and new gadgets introduced into the field of dentistry during the coronavirus pandemic worldwide. The relevant armamentarium is discussed under three broad headings, namely, those required before, during and after the procedures for easy understanding. RESULTS: A total of 15 gadgets and armamentarium related to oral and maxillofacial surgical practice are named and discussed in the literature review. DISCUSSION: We are particularly vulnerable to the transmission of diseases easily both due to the field of interest of work and type of instrumentation. Thus, we need to be extremely cautious about the procedure. Since, the literature is scarce about the sequelae of the coronavirus disease; shift to the automated, contactless gadgets is the way to look forward to a healthy dental practice. CONCLUSION: These gadgets are user friendly for any small dental set-up as well. The choice of these upgraded instruments are prerogative of the individual professionals according to their exclusive practice. Yet, the authors encourage all health care professionals to focus on better training in infection control and cross-contamination.

Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging.

Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated in vitro and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-α) and the upregulation of transforming growth factor beta (TGF-ß). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.

Reduction in Lesion Incidence in Pork Carcass Using Transdermal Needle-free Injection of Foot-and-Mouth Disease Vaccine.

Foot-and-mouth disease (FMD) is an infectious disease affecting pigs. The control of FMD in swine husbandry is very important because its outbreak results in a vast economic loss. FMD vaccination has effectively controlled FMD; however, it results in economic loss associated with the incidence of lesions in the pork meat at the injection site. The objective of this study was to investigate the effects of transdermal needle-free injection (NFI) of the FMD vaccine on the incidence of lesions at the injection site. Pigs (n=493) in the control group were vaccinated with the FMD vaccine using a commercial syringe needle, while 492 pigs in the transdermal NFI group received the FMD vaccine using a needle-free gas-powered jet injector. After the slaughter of the pigs, the incidence of lesions at the injection site of all pigs was checked by plant workers. The result of this study showed that the incidence of lesions in the pork ham from pigs vaccinated with NFI was 14.82% lower than that in control pigs (p<0.01). In addition, lesions generated in the NFI group were found just in the subcutaneous tissue. Therefore, the incidence of lesions at the injection site in pork from pigs vaccinated with the FMD vaccine can be effectively reduced by using transdermal NFI rather than a conventional syringe needle.

Alternative practices of achieving anaesthesia for dental procedures: a review.

Managing pain and anxiety in patients has always been an essential part of dentistry. To prevent pain, dentists administer local anaesthesia (LA) via a needle injection. Unfortunately, anxiety and fear that arise prior to and/or during injection remains a barrier for many children and adults from receiving dental treatment. There is a constant search for techniques to alleviate the invasive and painful nature of the needle injection. In recent years, researchers have developed alternative methods which enable dental anaesthesia to be less invasive and more patient-friendly. The aim of this review is to highlight the procedures and devices available which may replace the conventional needle-administered local anaesthesia. The most known alternative methods in providing anaesthesia in dentistry are: topical anaesthesia, electronic dental anaesthesia, jet-injectors, iontophoresis, and computerized control local anaesthesia delivery systems. Even though these procedures are well accepted by patients to date, it is the authors' opinion that the effectiveness practicality of such techniques in general dentistry is not without limitations.

Beta-glucan-loaded nanofiber dressing improves wound healing in diabetic mice.

The increased prevalence of chronic wounds requires novel treatment options. The aim of this study was to develop a beta-glucan (ßG)-loaded nanofiber wound dressing. Nanofibers were prepared using the needle-free Nanospider™ technology, an electrospinning method which enables the production of nanofibers at an industrial scale. The ßG was selected as active ingredient based on its confirmed wound healing potential in both animals and humans. Hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) were included as copolymers. Rheological profiles of spinning solutions containing HPMC, PEO, ßG, ethanol and water, were optimized. The nanofiber formation was confirmed by Field Emission Scanning Electron Microscopy (FE-SEM), and both nanofibers with (ßG-nanofibers) or without ßG (NoßG-nanofibers) were evaluated by their swelling index and FT-IR spectroscopy. The formulations, active ingredient and excipients were tested for their possible in vitro toxicity in keratinocytes. Finally, the wound healing potential of the nanofibers was tested in externally induced excisional wounds in male diabetic db/db mice. Three different doses of ßG-nanofibers and the ßG-free, NoßG-nanofibers, were evaluated for their in vivo wound healing efficacy. All nanofiber-treatments provided improved wound healing as compared to the negative control (water). All ßG-nanofiber treated groups exhibited significantly improved wound healing as compared to the NoßG-nanofiber treated group, indicating the potential of ßG-nanofibers as wound dressing.

Intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar protective immunity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine.

Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which erupts in the Asia-Pacific regions. A bivalent vaccine against both EV71 and CVA16 is highly desirable. In the present study, on the bases that an experimental bivalent vaccine comprising of inactivated EV71 and CVA16 induces a balanced protective immunity against both EV71 and CVA16, we compare the immunogenicity and reactogenicity of one fourth of a full dose of an intradermal vaccine administered by needle-free liquid jet injector with a full dose of an intramuscular vaccine administered by needle-syringe in monkeys. The results suggest that intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar immunogenicity and reactogenicity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine, regardless of whether monovalent or bivalent vaccines were used. Our results support the use of an intradermal bivalent vaccine strategy for HFMD vaccination in order to satisfy the requirements and reduce the costs.

Needle-free buccal anesthesia using iontophoresis and amino amide salts combined in a mucoadhesive formulation.

Iontophoresis is a strategy to increase the penetration of drugs through biological membranes; however, its use has been underexplored in mucosa. The aim of this work was to investigate the influence of iontophoresis in the mucosal penetration of prilocaine hydrochloride (PCL) and lidocaine hydrochloride (LCL), which are largely used in dentistry as local anesthetics, when combined in the same formulation. Semisolid hydrogels containing these drugs either alone or in combination were developed at two different pHs (7.0 and 5.8) and presented adequate mechanical and mucoadhesive properties for buccal administration. The distribution coefficients between the mucosa and the formulations (Dm/f) and the in vitro mucosa permeation and retention rates were evaluated for both PCL and LCL. At pH 7.0, the combination of the drugs decreased the Dm/f of PCL by approximately 3-fold but did not change the Dm/f of LCL; iontophoresis increased the permeation rate of PCL by 12-fold and did not significantly change LCL flux compared with the passive permeation rate of the combined drugs. Combining the drugs also resulted in an increase in both PCL (86-fold) and LCL (12-fold) accumulation in the mucosa after iontophoresis at pH 7.0 compared with iontophoresis of the isolated drugs. Therefore, applying iontophoresis to a semisolid formulation of this drug combination at pH 7.0 can serve as a needle-free strategy to speed the onset and prolong the duration of buccal anesthesia.

Needle-free transdermal delivery using PLGA nanoparticles: effect of particle size, injection pressure and syringe orifice diameter.

The aim of this study is to investigate the effects of particle size and other injection factors on the skin penetration of nanoparticles delivered with a needle-free injector. Experimental and simulation tests were carried out at various parameters. In addition to testing different sizes of nanoparticles, we also observed the effects of several injection pressures and syringe orifice diameters (SOD) on the dispersion pattern of the nanoparticles after injection. Our results showed that as the nanoparticle size increased from 45 nm to 452 nm, the resulting puncture opening, channel diameter, and depth of the nanoparticle dispersion decreased, but the width of the dispersion increased. Conversely, as the SOD increased, the puncture opening, channel diameter, and depth of the dispersion increased, but width of the dispersion decreased. Increasing the injection pressure also decreased the size, depth, and width of the puncture opening. These results identify how these three parameters affect nanoparticle delivery from a needle-free injector; therefore, our findings will be beneficial for optimization and further study of needle-free injectors as a mechanism for transdermal delivery of nanoparticles.

Primordium of an artificial Bruch's membrane made of nanofibers for engineering of retinal pigment epithelium cell monolayers.

Transplanted retinal pigment epithelium (RPE) cells hold promise for treatment of age-related macular degeneration (AMD) and Stargardt disease (SD), but it is conceivable that the degenerated host Bruch's membrane (BM) as a natural substrate for RPE might not optimally support transplanted cell survival with correct cellular organization. We fabricated novel ultrathin three-dimensional (3-D) nanofibrous membranes from collagen type I and poly(lactic-co-glycolic acid) (PLGA) by an advanced clinical-grade needle-free electrospinning process. The nanofibrillar 3-D networks closely mimicked the fibrillar architecture of the native inner collagenous layer of human BM. Human RPE cells grown on our nanofibrous membranes bore a striking resemblance to native human RPE. They exhibited a correctly orientated monolayer with a polygonal cell shape and abundant sheet-like microvilli on their apical surfaces. RPE cells built tight junctions and expressed RPE65 protein. Flat 2-D PLGA film and cover glass as controls delivered inferior RPE layers. Our nanofibrous membranes may imitate the natural BM to such extent that they allow for the engineering of an in vivo-like human RPE monolayer that maintains the natural biofunctional characteristics. Such ultrathin membranes may provide a promising vehicle for a functional RPE cell monolayer implantation in the subretinal space in patients with AMD or SD.