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Inhalation of iloprost, a stable prostacyclin analog, is an effective therapy for pulmonary hypertension with few side effects. This approach may, however, be handicapped by limitations of currently available nebulization devices. We assessed whether the physical characterization of a device is sufficient to predict drug deposition and pharmacologic effects. We investigated the effects of a standardized iloprost aerosol dose (5 μg; inhaled within approximately 10 min) in 12 patients with severe pulmonary hypertension in a crossover design employing three well-characterized nebulizers. The nebulizers use different techniques to increase efficiency and alveolar targeting (Ilo-Neb/Aerotrap [Nebu-Tec; Elsenfeld, Germany], Ventstream [MedicAid; Bognor Regis, UK], and HaloLite [Profile Therapeutics; Bognor Regis, UK]). Measurements were performed using a Swan-Ganz catheter and determination of arterial iloprost plasma levels. During inhalation of iloprost, the pulmonary vascular resistance decreased substantially (baseline, approximately 1,250 dyne·s·cm−5; decrease, − 35.5 to − 38.0%) and pulmonary artery pressure decreased substantially (baseline, approximately 58 mm Hg; decline, − 18.4 to −21.8%), whereas the systemic arterial pressure was largely unaffected. Cardiac output and mixed venous and arterial oxygen saturation displayed a marked increase. The pharmacodynamic profiles with the three devices were superimposable. Moreover, rapid entry of iloprost into the systemic circulation was noted, peaking immediately after termination of the inhalation maneuver, with very similar maximum serum concentrations (158 pg/mL, 155 pg/mL, and 157 pg/mL), and half-lives of serum levels (6.5 min, 9.4 min, and 7.7 min) for the three nebulizers, respectively. Interestingly, the “half-life” of the pharmacodynamic effects in the pulmonary vasculature (eg, decrease in pulmonary vascular resistance, ranging between 21 and 25 min) clearly outlasted this serum level-based pharmacokinetic half-life. A standardized dose of aerosolized iloprost delivered by different nebulizer types induces comparable pharmacodynamic and pharmacokinetic responses. Pulmonary vasodilation, persisting after disappearance of the drug from the systemic circulation, supports the hypothesis that local drug deposition largely contributes to the preferential pulmonary vasodilation in response to inhaled iloprost.

Central nervous system (CNS) disorders, such as psychiatric disorders, neurodegeneration, chronic pain, stroke, brain tumor, spinal cord injury, and many other CNS diseases, would hugely benefit from specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to the brain is challenging due to their low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit peptides’ clinical application and explain the interest in alternative routes of peptide administration, particularly nose-to-brain (N-to-B) delivery, which allows protein and peptide drugs to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure; the olfactory and trigeminal nerves provide a unique pathway to the brain and the external environment. This review highlights the intranasal delivery of drugs, focusing on peptide delivery, illustrating various clinical applications, nasal delivery devices, and the scope and limitations of this approach.

Purpose: The aim of the survey was to evaluate attitudes and perceptions toward nebulization therapy for the management of chronic obstructive pulmonary disease (COPD) in Indian population. Patients and methods: A cross-sectional, multicenter, quantitative survey was conducted from July to August 2019 among 103 COPD patients [>40 years, either gender, belonging to socio-economic class (SEC) A or SEC B] and their family caregivers. One-on-one interviews were conducted telephonically via an online survey platform (KoBo data collection tool) using a structured questionnaire. Patients receiving home nebulization were included, and the usage of nebulizers, satisfaction, and benefits and concerns with nebulizers were assessed. Results: Overall, 47% patients were on handheld inhalers + nebulizer, 54% used nebulizer for >8 weeks, and 27% used nebulizers daily for home maintenance. Majority of the patients (77%) were satisfied with nebulization therapy. Around 70% family caregivers opined that the quality of life of COPD patients improved post-nebulization therapy. The benefits of nebulizers perceived by patients were easier breathing (89%), feeling of well-being (86%), and ease of use (86%), while family caregivers reported reduced hospitalization (76%) and easier breathing (75%). Among those with prior experience with inhalers, 72% felt nebulizers gave long-term relief, while 65% perceived having immediate relief compared to inhaler. Overall, 61% opined that benefits with nebulizers outweighed the inconvenience associated with its use. Key concerns regarding nebulizers cited by patients were time- consuming procedure (50%), feeling of dependency (49%), and social embarrassment (48%), while family caregivers highlighted social embarrassment (45%) and multiple daily use (45%) as major concerns. Majority of the patients (73%) were compliant with their recommended frequency of the nebulizer. Conclusion: This first-of-its-kind survey highlights that the majority of patients and family caregivers were satisfied with nebulizers and reported improvements in symptoms and reduced hospitalizations with nebulizer therapy. The patients preferred nebulized therapy to inhalers. Keywords: nebulization, quality of life, home nebulization, nebulizer device, quantitative survey, satisfaction, patient perception, patient attitude

Flexible and wearable electronic devices hold great potential in electronic skins, health monitoring systems and soft robotics. Among them, flexible strain sensors with high performance are key components for wearable health monitoring devices. However, the facile and controllable preparation of highly sensitive sensors still faces significant challenges. By virtue of excellent conductivity of 2D transition metal carbids (MXenes), this work reports a facile and low‐cost fabrication strategy for large‐scale production of strain sensors. The sensitive layer is deposited on flexible interdigital electrodes by ultrasonic nebulization of Ti3C2Tx nanosheets. By controlling the nebulization time, different thicknesses of Ti3C2Tx films has a great influence on the performance of strain sensors. The Ti3C2Tx‐based strain sensor exhibits good sensing performances such as high GF (19.1) in the low strain range (≈0.25%–1.14%), short response time (0.7 s), and stable durability (over 1000 cycles). In practice, the potential applications of the strain sensor in sound frequency detection, human physiological signal monitoring and facial expression recognition are demonstrated. Finally, this work integrates the strain sensor with a miniaturized analyzer to assemble a wearable motion monitoring device for mobile healthcare. This study provides a facile strategy for fabricating flexible strain sensors in the field of wearable electronics. A facile fabrication method for large‐scale manufacture of strain sensors is developed. The strain sensors with good performance are prepared by utilizing ultrasonic nebulization to deposit Ti3C2Tx films onto a polyimide substrate. The strain sensors have numerous potential applications, including sound wave detection and physiological signal monitoring, making them a viable candidate for the development of wearable health monitoring devices.

Surface acoustic wave nebulization (SAWN) has recently been reported as a novel method to transfer non-volatile analytes directly from solution to the gas phase for mass spectrometric analysis. Here we present a comparison of the survival yield of SAWN versus electrospray ionization (ESI) produced ions. A series of substituted benzylpyridinium (BzPy) compounds were utilized to measure ion survival yield from which ion energetics were inferred. We also estimated bond dissociation energies using higher level quantum chemical calculations than previously reported for BzPy ions. Additionally, the effects on BzPy precursor ion survival of SAWN operational parameters such as inlet capillary temperature and solution flow-rate were investigated. Under all conditions tested, SAWN-generated BzPy ions displayed a higher tendency for survival and thus have lower internal energies than those formed by ESI.

Hyperhidrosis is a chronic disease characterized by increased sweat production. Local injections of botulinum toxin A (BTX-A) have been extensively used for treatment of primary hyperhidrosis (idiopathic). The current treatment for this condition involves several intradermal injections, resulting in poor patient compliance due to injection-related pain. Therefore, new protocols, including an improved anesthetic regimen, are required. We designed the present study to determine whether JetPeel™-3, a medical device used for transdermal delivery of drugs by jet nebulization, could be used to deliver lidocaine prior to the standard multiple BTX-A injections or deliver lidocaine together with BTX-A in order to determine the protocol giving better results in terms of procedure-related pain, sweating, and patient satisfaction in subjects affected by primary axillary, palmar or plantar hyperhidrosis. Twenty patients with a visual analog scale (VAS) sweating score ≥ 8 cm were randomized to receive lidocaine 2% (5 mL) delivered by JetPeel™-3 followed by multiple injections of BTX-A (100 units) or lidocaine 2% (5 mL) and BTX-A (50 units) delivered together by JetPeel™-3. Effect of treatment on sweating was measured by VAS (0= minimum sweating; 10= maximum sweating) at 3-month follow-up. Pain induced by the procedure was assessed by VAS (0= minimum pain; 10= maximum pain) immediately after the procedure. Patient satisfaction was assessed at 3-month follow-up using a 5-point scale (1= not at all satisfied; 2= not satisfied; 3= partially satisfied; 4= satisfied; 5= highly satisfied). Both treatment modalities reduced sweating at 3-month follow-up, if compared with baseline (all P<0.001). Delivery of lidocaine and BTX-A by JetPeel™-3 resulted in lower procedure-related pain and reduced sweating, if compared with lidocaine delivered by JetPeel™-3 followed by multiple BTX-A injections (all P<0.001). Patient satisfaction with the procedure was higher in the group receiving lidocaine and BTX-A treatment by JetPeel™-3, if compared with lidocaine delivered by JetPeel™-3 followed by multiple BTX-A injections (P<0.001). No side effects were observed in both groups. Lidocaine and BTX-A can be safely delivered together by JetPeel™-3 to treat primary palmar, plantar and axillary hyperhidrosis, resulting in lower procedure-related pain, improved sweating and higher patient satisfaction, if compared with lidocaine delivered by JetPeel™-3 followed by standard BTX-A injection therapy. Our protocol delivering lidocaine and BTX-A together by JetPeel™-3 requires a reduced quantity of BTX-A, further supporting the use of the transdermal drug delivery by jet nebulization over standard injection therapy for treatment of primary hyperhidrosis.

To determine the efficacy of a metered-dose inhaler (MDI) with a large spacer device as compared to nebulized wet aerosols in the treatment of an unselected population with severe airflow limitation. Randomized, double blind, placebo-controlled trial. University Hospital Department of Emergency Medicine (DEM). Fifty patients, referred to the DEM between October 1, 1994 and March 31, 1995 with a severe, acute obstructive pulmonary event. Thirteen patients were diagnosed as having COPD; 37 patients were diagnosed as having asthma. Patients received either placebo MDI through a 750-mL cone-shaped spacer (Glaxo) [2 puffs] and nebulized salbutamol aerosol 0.5 mL in 1.5 mL saline solution (group 1, n=25) or salbutamol MDI and 0.5 mL saline solution in 1.5 mL saline solution administered in the same manner as above (group 2, n=25). The above treatment was repeated three times every 15 min, unless side effects appeared. Upon enrollment into the study, the FEV1 in group 1 was 0.78±0.7 L (mean±SD), 32% of predicted, and in group 2, 0.74±0.51 L, 29% of predicted (p=0.83). The FEV1 values after the first, second, and third interventions were as follows: in group 1, 1.18±0.99 L, 1.40±0.8, and 1.47±0.79, respectively, and in group 2, 1.17±0.99 L, 1.46±1.01, and 1.54±0.79 (p=0.83, 0.36, and 0.48, respectively). We observed no difference in spirometric measurements between the two groups at any time. Even in the setting of the unselected group of patient referrals to the DEM for episodes of severe airflow limitation, the clinical and the objective bronchodilator responses to the administration of salbutamol are independent of the method of delivery: MDI with a large spacer vs aerosol nebulization.

To determine the efficacy of a metered-dose inhaler (MDI) with a large spacer device as compared to nebulized wet aerosols in the treatment of an unselected population with severe airflow limitation. Randomized, double blind, placebo-controlled trial. University Hospital Department of Emergency Medicine (DEM). Fifty patients, referred to the DEM between October 1, 1994 and March 31, 1995 with a severe, acute obstructive pulmonary event. Thirteen patients were diagnosed as having COPD; 37 patients were diagnosed as having asthma. Patients received either placebo MDI through a 750-mL cone-shaped spacer (Glaxo) [2 puffs] and nebulized salbutamol aerosol 0.5 mL in 1.5 mL saline solution (group 1, n=25) or salbutamol MDI and 0.5 mL saline solution in 1.5 mL saline solution administered in the same manner as above (group 2, n=25). The above treatment was repeated three times every 15 min, unless side effects appeared. Upon enrollment into the study, the FEV1 in group 1 was 0.78+/-0.7 L (mean+/-SD), 32% of predicted, and in group 2, 0.74+/-0.51 L, 29% of predicted (p=0.83). The FEV1 values after the first, second, and third interventions were as follows: in group 1, 1.18+/-0.99 L, 1.40+/-0.8, and 1.47+/-0.79, respectively, and in group 2, 1.17+/-0.99 L, 1.46+/-1.01, and 1.54+/-0.79 (p=0.83, 0.36, and 0.48, respectively). We observed no difference in spirometric measurements between the two groups at any time. Even in the setting of the unselected group of patient referrals to the DEM for episodes of severe airflow limitation, the clinical and the objective bronchodilator responses to the administration of salbutamol are independent of the method of delivery: MDI with a large spacer vs aerosol nebulization.

Background and objectives: Continuous albuterol nebulization (CAN) is a therapeutic modality available to treat status asthmaticus. Currently, CAN may be administered using a large-volume nebulizer (LVN) or a small-volume nebulizer attached to an infusion pump or refilled as needed. Few data are available regarding the reproducibility of aerosol characteristics during CAN. In this study, we determined the aerodynamic profile, drug output (DO), DO in respirable range (RD), solution output (SO), and changes in reservoir's albuterol concentration (AR) hourly during 4 hours of CAN. Design: A modified Puritan-Bennett 1600 jet nebulizer was tested with a large reservoir (LR; 250 mL), medium reservoir (MR; 45 mL), and small reservoir with infusion pump (SRP; 18 mL). We used 100-, 40-, and 4-mL initial fill volumes (with 10-mL/h infusion for SRP) of 1 mg/mL albuterol solution for the LR, MR, and SRP, respectively. Particle size distribution and DO consistency were determined by impaction and spectrophotometric analysis (275 nm). We also determined albuterol mass output. The SO was determined by gravimetric technique. Results: The PBsj produced a heterodisperse aerosol with a median mass aerodynamic diameter range of 1.8 to 2.2 μm. DO and RD paralleled SO. The LR had the highest SO, DO, and RD (8.03 ± 2.36 vs 5.73 ± 2.48 and 5.85 ± 0.51 mg/h for MR and SRP, respectively). The AR showed no statistically significant changes. Conclusions: The PBsj demonstrated consistent and adequate aerosol production during 4 hours of CAN. These bench data support the widespread use of a LVN for CAN. (CHEST 1998; 114:847–853) Abbreviations: AR=variation in reservoir's albuterol concentration expressed as albuterol ratio; CAN = continuous albuterol nebulization; DO=drug output; %DO=drug output expressed as percentage of first hour's drug output; GSD=geometric standard deviation; IP=infusion pump; LR=large reservoir; LVN=large-volume nebulizer; MMAD=mass median aerodynamic diameter; MR=medium reservoir; RD=respirable dose; %RR=percentage of particles in the 0.4 to 5-μm size range; SO=solution output; SRP=small reservoir with attached infusion pump; SVN =small-volume nebulizer

This chapter contains sections titled: Introduction Human Respiratory Tract and Aerosol Particle Deposition Therapeutic Indications for Aerosol Delivery Aerosol Drug Delivery Devices Metered Dose Inhalers Dry Powder Inhalers Nebulizers Emerging Technologies Conclusions References