Pullulan-Based Spray-Dried Mucoadhesive Microparticles for Sustained Oromucosal Drug Delivery.

Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 µm with an angle of repose values between 25.8-36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.

Particulate bioaerogels for respiratory drug delivery.

The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.

LncRNA-mediated cartilage homeostasis in osteoarthritis: a narrative review.

Osteoarthritis (OA) is a degenerative disease of cartilage that affects the quality of life and has increased in morbidity and mortality in recent years. Cartilage homeostasis and dysregulation are thought to be important mechanisms involved in the development of OA. Many studies suggest that lncRNAs are involved in cartilage homeostasis in OA and that lncRNAs can be used to diagnose or treat OA. Among the existing therapeutic regimens, lncRNAs are involved in drug-and nondrug-mediated therapeutic mechanisms and are expected to improve the mechanism of adverse effects or drug resistance. Moreover, targeted lncRNA therapy may also prevent or treat OA. The purpose of this review is to summarize the links between lncRNAs and cartilage homeostasis in OA. In addition, we review the potential applications of lncRNAs at multiple levels of adjuvant and targeted therapies. This review highlights that targeting lncRNAs may be a novel therapeutic strategy for improving and modulating cartilage homeostasis in OA patients.

Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation­induced cardiomyocyte injury based on network pharmacology and in vitro validation.

Liquiritin (LIQ) is a flavonoid known for its cardioprotective properties, extracted from Glycyrrhiza uralensis Fisch. The purpose of the present study was to investigate the protective mechanism of LIQ against hypoxia/reoxygenation (H/R) injury through in vitro experiments, with the goal of enhancing its pharmacological effects. Initially, network pharmacology was employed to explore the targets and mechanisms of LIQ. Subsequently, an in vitro H/R model was established using H9c2 cells. Potential targets for LIQ and myocardial ischemia-reperfusion injury (MIRI) were identified through online databases. The STRING, Cytoscape and DAVID databases were used to extract intersecting targets and mechanisms. In vitro experiments were conducted to validate these findings, assessing cardiac enzymes, oxidative stress indicators, mitochondrial fluorescence, apoptotic fluorescence, inflammation and related protein expression. The network pharmacological analysis revealed that the protective effects of LIQ on MIRI involve oxidative stress, inflammation and apoptosis. The results of in vitro experimental validation demonstrated that LIQ significantly reduced the activities of lactated dehydrogenase and creatine kinase isoenzyme-MB (P<0.05 or 0.01), as well as the level of malondialdehyde (P<0.01). It also inhibited the production of reactive oxygen species (P<0.01), the release of inflammatory factors (P<0.05 or 0.01) and apoptosis (P<0.01). By contrast, the LIQ pre-treatment group exhibited a significant increase in mitochondrial membrane potential level (P<0.05 or 0.01) and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (P<0.05 or 0.01). Furthermore, LIQ reduced the protein expressions of TNF-α receptor type 1 (TNFR1) and MMP9, along with the level of NF-κB phosphorylation (P<0.05 or 0.01). In conclusion, LIQ mitigated H/R-induced cardiomyocyte injury through mechanisms that may involve antioxidants, anti-apoptotic effects, protection against mitochondrial damage and suppression of inflammatory levels. These effects are achieved via inhibition of the TNFR1/NF-κB/MMP9 pathway.

Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer.

Cervical cancer is the second leading cause of morbidity and mortality in women worldwide. Traditional treatment methods have become limited. Naringenin, a flavonoid abundant in various fruits and herbal medicines, has demonstrated anti-tumor properties among other effects. This research undertook to elucidate the mechanism of naringenin in the context of cervical cancer treatment by leveraging network pharmacology and performing experimental validation. Initial steps involved predicting potential naringenin targets and subsequently screening for overlaps between these targets and those related to cervical cancer, followed by analysis of their interrelationships. Molecular docking was subsequently utilized to verify the binding effect of the central target. Within the framework of network pharmacology, it was discovered that naringenin might possess anti-cancer properties specific to cervical cancer. Following this, the anti-tumor effects of naringenin on Hela cell viability, migration, and invasion were assessed employing CCK-8, transwell, wound healing assays, and western blotting. Experimental data indicated that naringenin attenuates the migration and invasion of Hela cells via downregulation EGFR/PI3K/AKT signaling pathway. Thus, our findings suggest that naringenin has therapeutic impacts on cervical cancer via multiple mechanisms, primarily by inhibiting the migration and invasion through the EGFR/PI3K/AKT/mTOR pathway. This study offers fresh insights for future clinical studies.

LncRNAs in Kawasaki disease and Henoch-Schönlein purpura: mechanisms and clinical applications.

Kawasaki disease (KD) and Henoch-Schönlein purpura (HSP) are the two most predominant types of childhood vasculitis. In childhood vasculitis, factors such as lack of sensitive diagnostic indicators and adverse effects of drug therapy may cause multiorgan system involvement and complications and even death. Many studies suggest that long noncoding RNAs (lncRNAs) are involved in the mechanism of vasculitis development in children and can be used to diagnose or predict prognosis by lncRNAs. In existing drug therapies, lncRNAs are also involved in drug-mediated treatment mechanisms and are expected to improve drug toxicity. The aim of this review is to summarize the link between lncRNAs and the pathogenesis of KD and HSP. In addition, we review the potential applications of lncRNAs in multiple dimensions, such as diagnosis, treatment, and prognosis prediction. This review highlights that targeting lncRNAs may be a novel therapeutic strategy to improve and treat KD and HSP.

Effects of oral intake fruit or fruit extract on skin aging in healthy adults: a systematic review and Meta-analysis of randomized controlled trials.

Background: In recent years, oral various fruits or supplements of fruits natural extracts have been reported to have significant anti-aging effects on the skin (1, 2), However, despite many studies on this topic, there is often no clear evidence to support their efficacy and safety. In this paper, we present a comprehensive review and Meta-analysis of the evidence for the safety and efficacy of oral fruits and fruits extracts in improving skin aging. Methods: Four databases, Pubmed, Embase, Web of Science, and Cochrane Library (CENTRAL), were searched for relevant literature from 2000-01 to 2023-03. Seven randomized controlled trials (RCTs) of fruit intake or fruit extracts associated with anti-skin aging were screened for Meta-analysis. Results: Compared to placebo, oral intake of fruit or fruit extracts showed significant statistical differences in skin hydration and transepidermal water loss (TEWL), with a significant improvement in skin hydration and a significant decrease in TEWL. No significant statistical difference was observed in minimal erythema dose (MED), overall skin elasticity (R2), or wrinkle depth, and no evidence of significant improvement in skin condition was observed. Conclusion: Meta-analysis results suggest that consume administration of fruits or fruit extracts significantly enhances skin hydration and reduces transcutaneous water loss, but there is insufficient evidence to support other outcome recommendations, including minimal erythema dose (MED), overall skin elasticity(R2), and wrinkle depth. Systematic Review Registration: PROSPERO (york.ac.uk), identifier CRD42023410382.

Dual functional pullulan-based spray-dried microparticles for controlled pulmonary drug delivery.

Two main challenges are associated with current spray-dried microparticles for inhalation, including the enhancement of aerosolization performance of microparticles and the creation of sustained drug release for continuous treatment on-site. For achieving these purposes, pullulan was explored as a novel excipient to prepare spray-dried inhalable microparticles (with salbutamol sulphate, SS, as a model drug), which were further modified by additives of leucine (Leu), ammonium bicarbonate (AB), ethanol and acetone. It was demonstrated that all pullulan-based spray-dried microparticles had improved flowability and enhanced aerosolization behavior, with the fine particle (<4.46 µm) fraction of 42.0-68.7% w/w, much higher than 11.4% w/w of lactose-SS. Moreover, all modified microparticles showed augmented emitted fractions of 88.0-96.9% w/w, over 86.5% w/w of pullulan-SS. The pullulan-Leu-SS and pullulan-(AB)-SS microparticles demonstrated further increased fine particle (<1.66 µm) doses of 54.7 µg and 53.3 µg respectively, surpassing that (49.6 µg) of pullulan-SS, suggesting an additionally increased drug deposition in the deep lungs. Furthermore, pullulan-based microparticles revealed sustained drug release profiles with elongated time (60mins) over the control (2mins). Clearly, pullulan has a great potential to construct dual functional microparticles for inhalation with improved pulmonary delivery efficiency and sustained drug release on-site.

Mechanistic insights into the ameliorative effects of hypoxia-induced myocardial injury by Corydalis yanhusuo total alkaloids: based on network pharmacology and experiment verification.

Introduction: Corydalis yanhusuo total alkaloids (CYTA) are the primary active ingredients in yanhusuo, known for their analgesic and cardioprotective effects. However, the mechanisms underlying the treatment of Myocardial ischemia (MI) with CYTA have not been reported. The purpose of this study was to explore the protective effect of CYTA on MI and its related mechanisms. Methods: A network pharmacology was employed to shed light on the targets and mechanisms of CYTA's action on MI. The protective effect of CYTA against hypoxia damage was evaluated in H9c2 cells. Furthermore, the effects of CYTA on L-type Ca2+ current (ICa-L), contractile force, and Ca2+ transient in cardiomyocytes isolated from rats were investigated using the patch clamp technique and IonOptix system. The network pharmacology revealed that CYTA could regulate oxidative stress, apoptosis, and calcium signaling. Cellular experiments demonstrated that CYTA decreased levels of CK, LDH, and MDA, as well as ROS production and Ca2+ concentration. Additionally, CYTA improved apoptosis and increased the activities of SOD, CAT, and GSH-Px, along with the levels of ATP and Ca2+-ATPase content and mitochondrial membrane potential. Moreover, CYTA inhibited ICa-L, cell contraction, and Ca2+ transient in cardiomyocytes. Results: These findings suggest that CYTA has a protective effect on MI by inhibiting oxidative stress, mitochondrial damage, apoptosis and Ca2+ overload. Discussion: The results prove that CYTA might be a potential natural compound in the field of MI treatment, and also provide a new scientific basis for the its utilization.

Deep learning-based image reconstruction for photonic integrated interferometric imaging.

Photonic integrated interferometric imaging (PIII) is an emerging technique that uses far-field spatial coherence measurements to extract intensity information from a source to form an image. At present, low sampling rate and noise disturbance are the main factors hindering the development of this technology. This paper implements a deep learning-based method to improve image quality. Firstly, we propose a frequency-domain dataset generation method based on imaging principles. Secondly, spatial-frequency dual-domain fusion networks (SFDF-Nets) are presented for image reconstruction. We utilize normalized amplitude and phase to train networks, which reduces the difficulty of network training using complex data. SFDF-Nets can fuse multi-frame data captured by rotation sampling to increase the sampling rate and generate high-quality spatial images through dual-domain supervised learning and frequency domain fusion. Furthermore, we propose an inverse fast Fourier transform loss (IFFT loss) for network training in the frequency domain. Extensive experiments show that our method improves PSNR and SSIM by 5.64 dB and 0.20, respectively. Our method effectively improves the reconstructed image quality and opens a new dimension in interferometric imaging.

Gab2 promotes acute myeloid leukemia growth and migration through the SHP2-Erk-CREB signaling pathway.

Acute myeloid leukemia (AML) is a hematologic malignant disease largely affecting older adults with poor outcomes. Lack of effective targeted treatment is a major challenge in managing the disease in the clinic. Scaffolding adaptor Gab2 is amplified in a subset of AML. However, the causative role of Gab2 in AML remains to be explored. In this study, it was found that Gab2 was expressed at high levels in AML patient samples and AML cell lines. Experiments by knocking down Gab2 expression using shRNA showed that Gab2 promoted AML cell growth and migration in vitro and in vivo. Further studies using Gab2 mutants and pharmacological inhibitors revealed that Gab2 increased CREB phosphorylation via the SHP-2/Erk signaling pathway. CREB phosphorylation contributed to Gab2-induced cell migration by increasing MMP2 and MMP9 expression. This research indicates that high Gab2 expression promotes AML progression through the SHP2-Erk-CREB signaling pathway. CREB suppression may help treat AML with high Gab2 expression.

Enhanced cell affinity and osteogenic differentiation of liquid crystal-based substrate via surface bio-functionalization.

Regulation of cell-substrate interactions is an important factor for modulating cell behaviors. Tailoring the physical and chemical properties of the substrates to better mimic the extracellular matrix (ECM) of native tissue is a more effective strategy for enhancing the cell-substrate contact. In current work, we aim at improving surface bioactivity based on the liquid crystalline substrates for the enhancement in cell affinity and osteogenic differentiation. Polydopamine (PDOPA) adhesive coating was used as a reactive platform for the immobilization of chitooligosaccharide (COS) on the octyl hydroxypropyl cellulose ester (OPC) substrate to generate active OPC-PDOPA-COSs liquid crystalline substrates. Results demonstrated that PDOPA-coated OPC surfaces showed remarkably improved hydrophility and increased elastic modulus, leading to better initial cell attachment. Subsequent COS immobilization on the OPC-PDOPA layer could induce promotion of cell proliferation, polarization and cytoskeleton formation. Rat bone marrow mesenchymal stem cells (rBMSCs) seeded on the OPC-PDOPA-COSs showed higher alkaline phosphatase (ALP) activity, calcium deposition, and up-regulated bone-related genes expression, including BMP-2, RUNx-2, COL-I and OCN. In conclusion, surface biofunctionalization on the OPC-based liquid crystalline substrates could come into being the appropriate combination of surface chemistry and liquid crystalline characteristic that simulating in vivo ECM environment, resulting in a favorable support to enhance positive cell-substrate interactions.

Changes of serum uric acid and its clinical correlation in children with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is the most common type of childhood cardiomyopathy and uric acid (UA) is considered closely associated with cardiovascular disease. There are few reports about the relationship between serum UA level and DCM in children, and the present study aimed to analyze the changes and clinical correlation of the two. METHODS: The clinical data of 49 children under 16 years old and who were hospitalized with DCM, and 44 healthy children who underwent physical examination in the same period at Tianjin Children's Hospital from June 2015 to November 2019 were analyzed retrospectively. RESULTS: The 49 children in the case group included 17 males and 32 females, aged from 2 to 172 months. The case group were divided into New York Heart Association (NYHA) functional class I (n=2), class II (n=17), class III (n=11), and class IV (n=19). The 44 healthy children selected as the control group included 20 males and 24 females aged from 2 to 161 months. The serum UA level was detected, and an ultrasonic cardiogram was conducted in each child. The serum UA level, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left atrial diameter (LAD) of the case group were higher than that of the control group, while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower than that of the control group, and significant statistical differences were seen between the two groups (P<0.01). The serum UA level, LVEDD, LVESD, and LAD of NYHAIII-IV class patients were higher than that of the NYHAI-II class, but LVEF and LVFS were lower than that of the NYHA I-II class, and there were significant statistical differences between the two groups (P<0.01). Statistical correlations were seen between the serum UA level and NYHA functional class, LVEDD, LVESD, LAD, LVEF, and LVFS (rs=0.599, 0.567, 0.579, 0.475, -0.333, -0.341, respectively, P<0.05). CONCLUSIONS: Elevated serum UA levels exist in children with DCM and correlate with NYHA functional class and ultrasonic values. Change in serum UA levels may be used as a biomarker reflecting the severity of DCM in children.

Successful biosynthesis of natural antioxidant ergothioneine in Saccharomyces cerevisiae required only two genes from Grifola frondosa.

BACKGROUND: Ergothioneine (EGT) has a unique antioxidant ability and diverse beneficial effects on human health. But the content of EGT is very low in its natural producing organisms such as Mycobacterium smegmatis and mushrooms. Therefore, it is necessary to highly efficient heterologous production of EGT in food-grade yeasts such as Saccharomyces cerevisiae. RESULTS: Two EGT biosynthetic genes were cloned from the mushroom Grifola frondosa and successfully heterologously expressed in Saccharomyces cerevisiae EC1118 strain in this study. By optimization of the fermentation conditions of the engineered strain S. cerevisiae EC1118, the 11.80 mg/L of EGT production was obtained. With daily addition of 1% glycerol to the culture medium in the fermentation process, the EGT production of the engineered strain S. cerevisiae EC1118 can reach up to 20.61 mg/L. CONCLUSION: A successful EGT de novo biosynthetic system of S. cerevisiae containing only two genes from mushroom Grifola frondosa was developed in this study. This system provides promising prospects for the large scales production of EGT for human health.

Primaquine phosphate induces the apoptosis of ATRA-resistant acute promyelocytic leukemia cells by inhibition of the NF-κB pathway.

As a subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL) is characterized by a chromosomal translocation, most of which result in the production of a PML-RAR alpha fusion protein. Although the overall survival rate of APL patients has improved dramatically due to all-trans retinoic acid (ATRA) treatment, ATRA-resistance remains a clinical challenge in the management of APL. Therefore, alternative agents should be considered for ATRA-resistant APL patients. Here, we report that antimalaria drug primaquine phosphate (PRQ) exhibits an anti-leukemia effect on both ATRA-sensitive cell line NB4 and ATRA-resistant APL cell lines, NB4-LR2, NB4-LR1, and NB4-MR2. Moreover, PRQ significantly inhibited primary colony formation of untreated or relapsed APL patients. Further study showed that PRQ could induce the apoptosis of APL cells by inhibiting NF-κB signaling pathway. The in vivo study showed that PRQ significantly inhibited NB4-LR2 xenograft tumors growth. These results suggest that PRQ is a potential therapeutic agent for ATRA-resistant APL patients.

Preparation of Lipid-Peptide-DNA (LPD) Nanoparticles and Their Use for Gene Transfection.

Therapeutic gene delivery systems offer the potential for the treatment of a range of inherited and acquired inherited diseases. In contrast with viral gene vectors, the nonviral gene vectors provide a safer alternative and additional advantages such as the improved delivery efficiency, low cost, and often unlimited capacity to package DNA. Here we describe the preparation of a nonviral gene delivery technique based on lipid-peptide-DNA (LPD) complexes. The size of LPD particles is in the nanometer range. The use of these nanoparticulate LPDs results in high efficiency transfections and a high level of gene expression in vitro. LPDs provide a convenient and efficient tool for gene delivery in gene therapy.

Preparation of Spray-Dried Nanoparticles for Efficient Drug Delivery to the Lungs.

The use of nanoparticulate systems for pulmonary drug delivery offers a number of advantages including significantly improved delivery efficiency to deep lung and the improved bioavailability. The traditional nanoparticle manufacturing process such as ball/jet milling often yields large aggregates, which could detrimentally inhibit the effective delivery of drug particles to the lower respiratory tract. Here we report an alternative technique of spray-drying the microemulsions to produce nanoparticles (<100 nm) that can be dispersed homogenously in the propellant to form an extremely stable pressurized metered-dose inhaler (pMDI) formulations. Such nanoparticulate formulations provide an ideal tool for pulmonary drug delivery.

Anti-biofouling and functionalizable bioinspired chitosan-based hydrogel coating via surface photo-immobilization.

Zwitterionic polymer is a new generation of anti-fouling materials with its good resistance to protein and bacterial adhesion. Constructing the anti-fouling surfaces with zwitterionic polymer has been regarded as an effective approach for improving the biocompatibility and biofunctionality of clinic devices. Herein, we reported a facile approach to construct a biodegradable anti-biofouling and functionalizable hydrogel coating via photo-immobilization using commercial polyethylene terephthalate (PET) films as the substrate, based on zwitterionic glycidyl methacrylate-phosphorylcholine-chitosan (PCCs-GMA). The surface structure and physicochemical properties of zwitterionic PCCs-GMA hydrogel coating were investigated by X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM) and static water contact angle measurement, and its functionalizable sites were detected by fluorescence labeling. Compared with the pristine PET and cationic chitosan - GMA and hydroxypropyltrimethyl ammonium chloride chitosan (HTCC) - GMA hydrogel coatings, zwitterionic PCCs-GMA hydrogel coating exhibited excellent biocompatibility, and significantly reduced protein adsorption for three model proteins of fibrinogen, immunoglobulin and lysozyme, repelled platelet adhesion, as well as showed a high resistance to bacterial attachment of Escherichia coli and Staphylococcus aureus and superior anti-fouling properties to MRC-5 cells. The results indicated that photo-immobilized zwitterionic PCCs-GMA hydrogel coating has perspective as a dual functional platform with integrated antifouling and further biofunctional properties for various biomedical applications.

Time-of-flight secondary ion mass spectrometry analyses of vancomycin.

As an antibiotic that prevents and treats infections caused by Gram-positive bacteria such as Staphylococcus aureus, vancomycin incorporated in a biodegradable polymer poly(lactide-co-glycolide) provides opportunities to construct controlled-release drug delivery systems. Developments associated with this promising system have been largely concentrated on areas of drug delivery kinetics and biodegradability. In order to provide surface analytical approaches to this important system, the authors demonstrate applicability of time-of-flight secondary ion mass spectrometry (TOF-SIMS) in three-dimensional molecular imaging for a model system consisting of alternating layers of ploy(lactide-co-glycolide) and vancomycin. TOF-SIMS imaging clarified that the two chemicals can undergo phase separation when dimethyl sulfoxide is used as the solvent. The authors identified two diagnostic ions that are abundant and structural moieties of vancomycin. The results on TOF-SIMS imaging and depth profiling vancomycin provide useful information for further applications of TOF-SIMS in the development of antibiotic drug delivery systems involving the use of vancomycin.

Innovative pMDI formulations of spray-dried nanoparticles for efficient pulmonary drug delivery.

For drug delivery to the lungs, the aerodynamic size of drug particles plays a predominant role in determining the sites of deposition in the airway, and the particles with the size less than 2µm are highly expected as they will be preferably delivered to the ideal site of alveolar regions. In this paper, a novel platform technology has been developed, where the water (containing pharmaceutically active agents)-in-oil (w/o) microemulsions were spray-dried to generate nanosized drug particles that were able to be homogeneously dispersed in the propellant to form an exceptionally stable suspensions with no precipitates or flocculates during a long time storage. High fine particle (<5.8µm) fraction (∼70% w/w) was achieved, irrespectively of drug molecular size and storage time. This platform technology works pretty well on chemical drugs (i.e. salbutamol sulphate) and biotherapeutics (i.e. insulin) for the generation of nanoparticles, and the nanoparticle pMDI formulations were homogeneous, stable and of high delivery efficiency to the lungs, representing an ideal way for pulmonary delivery.