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29 pages, 12096 KB  
Article
Lecithin-Coated PLGA Nanoparticles for Pulmonary Targeting of Naringin: Formulation, Optimization and In Vitro Characterization
by Pooja Dattatray Deshmane, Sanjeevani Shekhar Deshkar, Avinash Kharat, Ramesh Bhonde, Ravindra Wavhale and Prabhanjan Giram
Int. J. Mol. Sci. 2026, 27(11), 5095; https://doi.org/10.3390/ijms27115095 - 4 Jun 2026
Viewed by 454
Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and chronic airway inflammation. Current therapeutic strategies primarily offer symptomatic relief and are often limited by systemic side effects, inadequate lung deposition, and poor patient compliance. Naringin (NAR), a natural flavonoid with strong antioxidant, anti-inflammatory, and anti-fibrotic activities, has demonstrated potential in mitigating COPD-associated pathophysiology. However, its therapeutic application is restricted by poor water solubility, low bioavailability, and rapid metabolism. Nanotechnology-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, provide an effective approach for lung-targeted therapy. Their nanoscale size promotes deep lung deposition, enhanced cellular uptake, reduced lung clearance, improved therapeutic efficacy, and reduced systemic side effects. The present study aimed to develop NAR-loaded PLGA nanoparticles (NAR PLGA NP) for enhanced cell-targeting in inflammatory lung conditions. NAR PLGA NP were prepared using the emulsion solvent evaporation method, with PLGA in the organic phase and soya lecithin (SL) with poly(vinyl alcohol) (PVA) as surfactants in the aqueous phase. A face-centered central composite design was employed to optimize the formulation. The optimized nanoparticles were characterized for size distribution by dynamic light scattering, entrapment efficiency, Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), and in vitro drug release. The safety of PLGA and lecithin-coated PLGA nanoparticles (LC PLGA NP) was assessed using an MTT assay on lung epithelial cells, followed by cellular uptake studies, angiogenesis by chick Yolk Sac Membrane (YSM) assay, and in vitro evaluation of reactive oxidative stress (ROS) and anti-inflammatory activity. The optimized PLGA formulation showed a hydrodynamic diameter of 201 ± 1 nm with PDI 0.20 ± 0.03 and EE of 76.11 ± 2.1%, and 81.7 ± 4.9% drug release at 72 h, whereas LC PLGA NP showed a hydrodynamic diameter of 308 ± 3 nm, PDI of 0.21 ± 0.05, entrapment efficiency of 82.45 ± 4.8%, and 71.4 ± 3.2% drug release at 72 h. Both PLGA NP and LC PLGA NP demonstrated good cytocompatibility with lung epithelial cells, efficient cellular uptake, and a significant reduction in intracellular reactive oxygen species (ROS) levels (**** p value < 0.0001). Moreover, the formulations markedly suppressed pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, indicating anti-inflammatory activity. The angiogenesis assay further suggested their ability for lung tissue repair and remodeling. These findings support the potential of LC PLGA NP as a promising cell-specific targeting system for naringin in inflammatory lung conditions. Full article
(This article belongs to the Special Issue Advances in Polymeric Nanomaterials in Medicine)
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26 pages, 7428 KB  
Article
Terpene-Enriched Nitazoxanide-Loaded Chondrosomes: Aerodynamic Characterization and In Silico Evaluation of Antiviral Activity
by Rofida Albash, Anroop B. Nair, Mohamed A. Morsy, Katharigatta N. Venugopala, Pottathil Shinu, Amira B. Kassem, Asmaa Saleh and Moaz A. Eltabeeb
Pharmaceuticals 2026, 19(5), 702; https://doi.org/10.3390/ph19050702 - 29 Apr 2026
Viewed by 593
Abstract
Background/Objectives: This investigation aims to assess the potential for repurposing nitazoxanide (NIT) as a treatment for COVID-19. NIT was loaded into terpene-enriched chondrosomes (TECs) to assess its anti-hCoV-19 activity through pulmonary delivery. Methods: NIT-TECs were then fabricated utilizing the ethanol injection method. [...] Read more.
Background/Objectives: This investigation aims to assess the potential for repurposing nitazoxanide (NIT) as a treatment for COVID-19. NIT was loaded into terpene-enriched chondrosomes (TECs) to assess its anti-hCoV-19 activity through pulmonary delivery. Methods: NIT-TECs were then fabricated utilizing the ethanol injection method. Using a D-optimal design, the effects of factors on entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) were determined, and the optimal formulation was selected. Results: The optimum TEC exhibited an EE% of 98.87 ± 0.69, a PS of 129.43 ± 5.43 nm, a polydispersity index (PDI) of 0.433 ± 0.022, and a ZP of −25.99 ± 0.99 mV. The optimum TEC was lyophilized to attain a dry powder. Further, the differential scanning calorimetry test confirmed that NIT was transformed from crystalline to amorphous form inside the optimum TEC. In addition, the mucoadhesion test confirmed the ability of the optimum TECs to adhere to pulmonary tissues. Additionally, NIT binding to the active site of SARS-CoV-2 enzymes was investigated using in silico analysis. When compared to NIT, the aerodynamic characteristics of the lyophilized optimum TECs employing the cascade impactor showed superior residence in the lungs. Conclusions: These findings suggest that loading NIT into TECs enhanced its antiviral activity, as indicated by the in vitro cytotoxicity study. Overall, the results point to NIT-loaded TECs as a potentially effective pulmonary delivery system for COVID-19 treatment. Full article
(This article belongs to the Special Issue Application of Nanotechnology in Drug Delivery)
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15 pages, 3690 KB  
Article
Plasma Fibronectin Drives Macrophage Elongation via Integrin β3–Tie2 Axis in Blood Clots
by Lynn M. Knowles, Hermann Eichler and Jan Pilch
Cancers 2025, 17(23), 3780; https://doi.org/10.3390/cancers17233780 - 26 Nov 2025
Viewed by 808
Abstract
Background/Objectives: Plasma fibronectin (pFN) supports lung metastasis by promoting tumor cell invasion and survival in the context of blood clotting. Here, we set out to test if myeloid cells reiterate the clot-invasive mechanisms that have been established for tumor cells. Methods: We [...] Read more.
Background/Objectives: Plasma fibronectin (pFN) supports lung metastasis by promoting tumor cell invasion and survival in the context of blood clotting. Here, we set out to test if myeloid cells reiterate the clot-invasive mechanisms that have been established for tumor cells. Methods: We analyzed lung tissue sections from transgenic pFN-deficient mice for the co-localization of intravenously injected B16F1 tumor cells and the surrounding fibrin with myeloid cells, granulocytes, and macrophages. We also tested the role of pFN for macrophage differentiation and invasion in a three-dimensional fibrin matrix. Results: B16F1 melanoma cells, entrapped in the lungs of pFN-competent C57BL/6-Fn(fl/fl)Mx-Cre mice, were surrounded by a fibrin matrix, CD11b-positive myeloid cells, and Gr-1-positive granulocytes within 1 h of intravenous injection, while homing F4/80-positive macrophages to lung-born tumor cells occurred within 16 h. Compared to pFN-competent C57BL/6-Fn(fl/fl)Mx-Cre mice, the co-localization of CD11b+, Gr-1+, and F4/80+ cells with B16F1 cells was significantly reduced in the lungs of pFN-deficient C57BL/6-Fn(fl/fl)Mx-Cre mice. Mechanistically, we found that fibrin–fibronectin complexes promoted macrophage adhesion, differentiation, and invasion in clotted plasma. The pro-invasive function of fibrin–fibronectin depended on the upregulation of integrin β3 and Tie2 expression in macrophages and was reversed after knocking-down integrin β3 and Tie2 with siRNA. Conclusions: Our results suggest that blood clotting plays an important role in the recruitment of macrophages to circulating tumor cells and that the underlying mechanism of macrophage recruitment involves fibrin–fibronectin complexes, integrin β3, and Tie2. Full article
(This article belongs to the Section Cancer Metastasis)
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18 pages, 978 KB  
Review
Pediatric Asthma in the Inland Empire: Environmental Burden, Gaps in Preventive Care, and Unmet Needs
by Catherine Kim, Christine Gharib and Hani Atamna
Children 2025, 12(9), 1183; https://doi.org/10.3390/children12091183 - 4 Sep 2025
Cited by 1 | Viewed by 3095
Abstract
Background: Asthma is the most prevalent chronic illness in children worldwide, contributing to significant morbidity, health care utilization, and economic burden. In the United States, approximately five million children are affected by asthma. This review explores the environmental contexts and lifestyle determinants of [...] Read more.
Background: Asthma is the most prevalent chronic illness in children worldwide, contributing to significant morbidity, health care utilization, and economic burden. In the United States, approximately five million children are affected by asthma. This review explores the environmental contexts and lifestyle determinants of pediatric asthma, with a focus on the Inland Empire (IE) region of Southern California. The IE’s unique geographic landscape and importance as a major transportation hub highlights its critical role for understanding how both environmental and structural factors exacerbate asthma burden within the pediatric population. Variables such as household income, parental education levels, and lack of community-based asthma programs were explored. Despite significant burdens, the IE remains under-represented in asthma research, contributing to persistent disparity. Methods: A narrative literature review and regional data analysis were conducted via PubMed, Scopus, and Google Scholar (2000–2025), alongside data from the CDC, CDPH, and American Lung Association. Key words used included “pediatric asthma, Inland Empire, air pollution, asthma disparity, emergency department utilization, socioeconomic status.” Inclusion criteria were: (1) studies or reports focusing on pediatric asthma (ages 0–17), (2) articles addressing environmental, socioeconomic, or health care-related risk factors, and (3) research with either national, state-level, or IE-specific data. Exclusion criteria were: (1) articles not in English, adult-only asthma studies, and (3) publications without original data or reference to pediatric asthma burden, management, or outcomes. Titles and abstracts were screened for relevance, and full texts were reviewed when abstracts met inclusion criteria. A total of 61 studies, reports, and data sources met this criterion and were included into this review. Results: The IE—comprised of San Bernardino (SB) and Riverside Counties— is home to four of the top five most polluted cities in North America. Vehicle emissions and industrial waste are concentrated in the region due to limited air circulation from surrounding mountains that entrap pollutants. Pediatric asthma ED visit rates in SB and Riverside were 60.5% and 59.3%, compared to California’s average of 56.7%. Hospitalization rates for children aged 0–4 were also higher in SB (24.4%) compared to the state average (17.3%). The elevated rates among school-aged children underscore the crucial need for interventions aimed at improving air quality, enhancing asthma management, and increasing access to preventive health care. Conclusions: Pediatric asthma in the IE reflects heightened environmental risks, socioeconomic barriers, and gaps in health care access. Addressing these disparities requires targeted interventions, policies, and region-specific research to enhance long-term management strategies and outcomes for vulnerable pediatric populations. Full article
(This article belongs to the Section Pediatric Allergy and Immunology)
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11 pages, 1172 KB  
Article
Optimizing Photosensitizer Delivery for Effective Photodynamic Inactivation of Klebsiella pneumoniae Under Lung Surfactant Conditions
by Fernanda Alves, Isabelle Almeida de Lima, Lorraine Gabriele Fiuza, Zoe A. Arnaut, Natalia Mayumi Inada and Vanderlei Salvador Bagnato
Pathogens 2025, 14(7), 618; https://doi.org/10.3390/pathogens14070618 - 21 Jun 2025
Cited by 2 | Viewed by 1786
Abstract
Klebsiella pneumoniae is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a [...] Read more.
Klebsiella pneumoniae is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a broad spectrum of action and multiple molecular targets, and has been proposed for the treatment of clinically relevant infections such as pneumonia. However, despite excellent in vitro photodynamic inactivation outcomes, the success of in vivo therapy still faces challenges, particularly due to the presence of lung surfactant (LS) in the alveoli. LS entraps photosensitizers, preventing these molecules from reaching microbial targets. This study investigated the potential of indocyanine green (ICG) in combination with the biocompatible polymer Gantrez™ AN-139 for the photoinactivation of K. pneumoniae. Initial in vitro experiments demonstrated that aPDT with ICG alone is effective against K. pneumoniae in a concentration- and light dose-dependent manner, achieving total eradication at 75 µg/mL of ICG and 150 J/cm2 of 808 nm light. When aPDT was performed with similar parameters in the presence of LS, no bacterial killing was observed. However, a significant synergistic effect was observed when ICG (25 µg/mL) was combined with a low concentration of Gantrez™ AN-139 (0.5% m/v) in the presence of dipalmitoylphosphatidylcholine (DPPC), the main component of LS. This formulation resulted in a substantial reduction (3.6 log10) in K. pneumoniae viability. These findings highlight the potential of Gantrez™ AN-139 as an efficient carrier to enhance the efficacy of ICG-mediated aPDT against K. pneumoniae, even in the presence of lung surfactant, a necessary step before the in vivo experiments. Full article
(This article belongs to the Special Issue Bacterial Pathogenesis and Antibiotic Resistance)
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18 pages, 4037 KB  
Article
Voriconazole-Loaded Nanohydrogels Towards Optimized Antifungal Therapy for Cystic Fibrosis Patients
by Shaul D. Cemal, María F. Ladetto, Katherine Hermida Alava, Gila Kazimirsky, Marcela Cucher, Romina J. Glisoni, María L. Cuestas and Gerardo Byk
Pharmaceutics 2025, 17(6), 725; https://doi.org/10.3390/pharmaceutics17060725 - 30 May 2025
Cited by 2 | Viewed by 1580
Abstract
Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. [...] Read more.
Background/Objectives: Filamentous fungi, in particular the species Aspergillus, Scedosporium, and Exophiala, frequently colonize the lungs of cystic fibrosis (CF) patients. Chronic colonization is linked to hypersensitivity reactions and persistent infections leading to a significant long-term decline in lung function. Azole antifungal therapy such as voriconazole (VRC) slows disease progression, particularly in patients with advanced CF; however, excessive mucus production in CF lungs poses a diffusional barrier to effective treatment. Methods: Here, biodegradable nanohydrogels (NHGs) recently developed as nanocarriers were evaluated for formulating VRC as a platform for treating fungal infections in CF lungs. The NHGs entrapped up to about 30 μg/mg of VRC, and physicochemical properties were investigated via dynamic laser light scattering and nanoparticle tracking analysis. Diameters were 100–400 nm, and excellent colloidal stability was demonstrated in interstitial fluids, indicating potential for pulmonary delivery. Nano-formulations exhibited high in vitro cytocompatibility in A549 and HEK293T cells and were tested for the release of VRC under two different sink conditions. Results: Notably, the antifungal activity of VRC-loaded nanohydrogels was up to eight-fold greater than an aqueous suspension drug against different fungal species isolated from CF sputum, regardless of the presence of a CF artificial mucus layer. Conclusions: These findings support the development of potent VRC nano-formulations for treating fungal disorders in CF lungs. Full article
(This article belongs to the Special Issue Nanoparticle-Mediated Targeted Drug Delivery Systems)
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26 pages, 6909 KB  
Article
Development of Voriconazole Proliposome Based Dry Powder for Inhalation: A Design of Experiment Approach
by Sanjeevani Deshkar, Alisha Vas, Roshani Pagar, Prabhanjan Giram, Asha Thomas and Vaishali Undale
Pharmaceutics 2025, 17(5), 622; https://doi.org/10.3390/pharmaceutics17050622 - 8 May 2025
Cited by 4 | Viewed by 2182
Abstract
The present investigation aimed to formulate and optimize sustained release proliposome dry powder for inhalation of Voriconazole (VZ) and its in vitro and in vivo evaluation. The proliposome-based dry powder for inhalation was formulated by spray drying technique using Phospholipon 90H and cholesterol [...] Read more.
The present investigation aimed to formulate and optimize sustained release proliposome dry powder for inhalation of Voriconazole (VZ) and its in vitro and in vivo evaluation. The proliposome-based dry powder for inhalation was formulated by spray drying technique using Phospholipon 90H and cholesterol in the lipid phase, mannitol as a carrier, and L-leucine as a dispersing agent. A face-centered central composite design was used to study the influence of factors on responses, vesicle size, VZ entrapment efficiency, and drug release. The optimized formulation was further characterized by FTIR, FESEM, DSC, XRD, and evaluated for in vitro drug release, in vitro aerosol deposition, and in vivo lung retention study in Wistar rats. For the optimized batch F-5 proliposome formulation, vesicle size was observed as 191.7 ± 0.049 nm with PDI 0.328 ± 0.009, entrapment efficiency as 72.94 ± 0.56%, and cumulative drug release after 8 h of dissolution was 82.0 ± 0.14%. The median mass aerodynamic diameter (MMAD) generated by optimized formulation F5 was significantly lower (3.85 ± 0.15 µm, p < 0.0001) as compared to spray-dried voriconazole (SD-VZ) (8.35 ± 0.23 µm). In vivo studies demonstrated a profound enhancement in lung retention (3.8-fold) compared to SD-VZ and oral VZ dispersion. Conclusively, proliposome formulation of voriconazole is a plausible and convincing approach for pulmonary fungal infections, considering its sustained release behaviour and prolonged lung retention. Full article
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29 pages, 3369 KB  
Review
Thoracic Ultrasound for Pre-Procedural Dynamic Assessment of Non-Expandable Lung: A Non-Invasive, Real-Time and Multifaceted Diagnostic Tool
by Guido Marchi, Federico Cucchiara, Alessio Gregori, Giulia Biondi, Giacomo Guglielmi, Massimiliano Serradori, Marco Gherardi, Luciano Gabbrielli, Francesco Pistelli and Laura Carrozzi
J. Clin. Med. 2025, 14(6), 2062; https://doi.org/10.3390/jcm14062062 - 18 Mar 2025
Cited by 12 | Viewed by 3426
Abstract
Non-expandable lung (NEL) occurs when the lung fails to fully re-expand after pleural fluid drainage, complicating management and limiting therapeutic options. Diagnosis, based on clinical symptoms, pleural manometry, and traditional imaging, is often delayed to the peri- or post-procedural stages, leading to improper [...] Read more.
Non-expandable lung (NEL) occurs when the lung fails to fully re-expand after pleural fluid drainage, complicating management and limiting therapeutic options. Diagnosis, based on clinical symptoms, pleural manometry, and traditional imaging, is often delayed to the peri- or post-procedural stages, leading to improper management, complications, and higher healthcare costs. Therefore, early, pre-procedural diagnostic methods are needed. Thoracic ultrasound (TUS) has emerged as a non-invasive tool with the potential to enhance diagnostic accuracy and guide clinical decisions, yet, it remains inadequately studied within the context of NEL. We conducted a non-systematic narrative review using a structured methodology, including a comprehensive database search, predefined inclusion criteria, and QUADAS-2 quality assessment. This approach ensured a rigorous synthesis of evidence on TUS in NEL, with the aim of identifying knowledge gaps and guiding future studies. Non-invasive, real-time, bedside M-mode TUS has demonstrated efficacy in predicting NEL prior to thoracentesis by detecting an absent sinusoidal sign and reduced atelectatic lung movement. Emerging experimental techniques, including 2D shear wave elastography (SWE), speckle tracking imaging (STI) strain analysis, the lung/liver echogenicity (LLE) ratio, TUS assessment of dynamic air bronchograms, and pleural thickening evaluation, show additional potential to enhance pre-procedural NEL detection. However, all these methods have significant limitations that require further comprehensive investigation. Despite their significant promise, TUS modalities for early NEL detection still require rigorous validation and standardization before broad clinical use. A multimodal diagnostic approach, combining clinical manifestations, pleural manometry, radiologic and ultrasonographic findings, along with emerging techniques (once fully validated), may provide the most extensive framework for NEL. Regardless of advancements, patient-centered care and shared decision-making remain essential. Further research is needed to improve outcomes, reduce healthcare costs, and enhance long-term treatment strategies. Full article
(This article belongs to the Special Issue Interventional Pulmonology: Advances and Future Directions)
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19 pages, 2176 KB  
Article
Evaluating the Immunogenicity of an Intranasal Microparticle Combination Vaccine for COVID-19 and Influenza
by Sharon Vijayanand, Smital Patil, Priyal Bagwe, Revanth Singh, Emmanuel Adediran and Martin J. D’Souza
Vaccines 2025, 13(3), 282; https://doi.org/10.3390/vaccines13030282 - 7 Mar 2025
Cited by 2 | Viewed by 3033
Abstract
Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination [...] Read more.
Background: Infectious respiratory pathogens like SARS-CoV-2 and influenza frequently mutate, leading to the emergence of variants. This necessitates continuous updates to FDA-approved vaccines with booster shots targeting the circulating variants. Vaccine hesitancy and needle injections create inconvenience and contribute to reduced global vaccination rates. To address the burden of frequent painful injections, this manuscript explores the potential of non-invasive intranasal (IN) vaccine administration as an effective alternative to intramuscular (IM) shots. Further, as a proof-of-concept, an inactivated combination vaccine for COVID-19 and influenza was tested to eliminate the need for separate vaccinations. Methods: The methods involved encapsulating antigens and adjuvants in poly(lactic-co-glycolic acid) (PLGA) polymer matrices, achieving over 85% entrapment. The vaccine was evaluated in vitro for cytotoxicity and immunogenicity before being administered to 6–8-week-old Swiss Webster mice at weeks 0, 3, and 6. The mice were then assessed for antibody levels and cellular responses. Results: The intranasal microparticle (IN-MP) vaccine induced an innate immune response, autophagy, and were non-cytotoxic in vitro. In vivo, the vaccine led to high levels of virus-specific serum IgM, IgG, and IgA binding antibodies, as well as elevated IgG and IgA levels in the lung wash samples. The antibodies generated demonstrated neutralizing activity against the SARS-CoV-2 pseudovirus. Furthermore, the IN-MP vaccine prompted increased antigen-specific CD4+ and CD8+ T-cell responses in the vaccinated mice. Conclusions: The IN-MP combination vaccine produced immune responses comparable to or higher than the IM route, indicating its potential as an alternative to IM injections. Full article
(This article belongs to the Special Issue Innovating Vaccine Research in Mucosal Vaccines)
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15 pages, 2240 KB  
Article
Mesoporous Polydopamine Nano-Bowls Demonstrate a High Entrapment Efficiency and pH-Responsive Release of Paclitaxel for Suppressing A549 Lung Cancer Cell Proliferation In Vitro
by Lindokuhle M. Ngema, Shahinur Acter, Samson A. Adeyemi, Thashree Marimuthu, Mershen Govender, Wilfred Ngwa and Yahya E. Choonara
Pharmaceutics 2024, 16(12), 1536; https://doi.org/10.3390/pharmaceutics16121536 - 1 Dec 2024
Cited by 7 | Viewed by 3100
Abstract
Background: The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical [...] Read more.
Background: The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy. Methods: The present study describes the fabrication of mesoporous polydopamine (mPDA) nano-bowls via an emulsion-induced interfacial anisotropic assembly method, designed for efficient entrapment of PTX and pH-responsive release behaviour. Results: The nano-bowls depicted a typical bowl-like shape, with connecting mesoporous channels and a central hollow cavity, allowing optimal loading of PTX. The fabricated nanocarrier system, mPDA-PTX-nb, had a mean hydrodynamic bowl diameter of 200.4 ± 5.2 nm and a surface charge of −39.2 ± 1.3 mV. The entrapment efficiency of PTX within the nano-bowls was found to be 95.7%, with a corresponding release of 85.1% achieved at the acidic pH 5.9 (simulated tumour microenvironment) at 48 h. Drug release was best fitted to the Peppas–Sahlin model, indicating the involvement of both diffusion and relaxation mechanisms. Treatment with mPDA-PTX-nb significantly suppressed A549 lung cancer cell proliferation at 48 and 72 h, resulting in cell viability of 14.0% and 9.3%, respectively, at the highest concentration (100 µg/mL). Conclusions: These results highlight the potential of mPDA-PTX-nb as an effective nanocarrier for PTX, promoting enhanced anti-proliferative effects in NSCLC therapy. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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19 pages, 6392 KB  
Article
A Bait-and-Hook Hydrogel for Net Tumor Cells to Enhance Chemotherapy and Mitigate Metastatic Dissemination
by Cailian Chen, Jinying Liu, Hongbo Zhang, Hongrui Zhang, Yanhui Liang, Qilian Ye, Wei Shen, Haibin Luo and Ling Guo
Pharmaceutics 2024, 16(12), 1516; https://doi.org/10.3390/pharmaceutics16121516 - 25 Nov 2024
Cited by 4 | Viewed by 1848
Abstract
Background: Lung cancer is an aggressive disease with rapid progression and a high rate of metastasis, leading to a significantly poor prognosis for many patients. While chemotherapy continues to serve as a cornerstone treatment for a large proportion of lung cancer patients, [...] Read more.
Background: Lung cancer is an aggressive disease with rapid progression and a high rate of metastasis, leading to a significantly poor prognosis for many patients. While chemotherapy continues to serve as a cornerstone treatment for a large proportion of lung cancer patients, expanding preclinical and clinical evidence indicates that chemotherapy may promote tumor metastasis and cause side effects. Methods: We develop an injectable bait-and-hook hydrogel (BH-gel) for targeted tumor cell eradication, which embedded doxorubicin liposomes as cytotoxic agents and CXCL12 as a chemoattractant to capture and kill tumor cells. The hydrogel backbone was formed through covalent cross-linking between PVA and borax. In vitro, we investigated tumor recruitment and the antitumor effects in A549 cells. In vivo, we explored the anti-metastatic and antitumor activities against lung cancer. Results: BH-gel retained CXCL12 within its three-dimensional porous architecture for gradual release, effectively recruiting tumor cells. In contrast, blank hydrogel failed to achieve this. After encapsulation in BH-gel, the therapeutic efficacy of doxorubicin liposomes for tumor eradication was markedly improved, significantly reducing metastatic tumor presence to near-undetectable levels, while also resulting in notable reductions in cardiotoxicity and hepatotoxicity. Notably, BH-gel adhered well to tissues and exhibited exceptional electrical conductivity, which may be further developed into a real-time tumor monitoring system, facilitating timely therapeutic adjustments. Conclusions: BH-gel utilizes CXCL12 as a bait to recruit and entrap tumor cells in a three-dimensional porous matrix and subsequently kill them with embedded doxorubicin liposomes, thereby tackling the issue of metastatic spread. This bait-and-hook strategy has significant implications for the field of anti-metastasis medicine and shows considerable potential for clinical application. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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20 pages, 1817 KB  
Article
Intratracheal Administration of Itraconazole-Loaded Hyaluronated Glycerosomes as a Promising Nanoplatform for the Treatment of Lung Cancer: Formulation, Physiochemical, and In Vivo Distribution
by Sultan Aati, Hanan O. Farouk, Marwa H. Elkarmalawy, Hanan Y. Aati, Nahla Sameh Tolba, Hossam M. Hassan, Mostafa E. Rateb and Doaa S. Hamad
Pharmaceutics 2024, 16(11), 1432; https://doi.org/10.3390/pharmaceutics16111432 - 10 Nov 2024
Cited by 6 | Viewed by 3093
Abstract
Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), [...] Read more.
Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Respiratory Diseases)
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19 pages, 6476 KB  
Article
Preparing a Phytosome for Promoting Delivery Efficiency and Biological Activities of Methyl Jasmonate-Treated Dendropanax morbifera Adventitious Root Extract (DMARE)
by Fengjiao Xu, Shican Xu, Li Yang, Aili Qu, Dongbin Li, Minfen Yu, Yongping Wu, Shaojian Zheng, Xiao Ruan and Qiang Wang
Biomolecules 2024, 14(10), 1273; https://doi.org/10.3390/biom14101273 - 10 Oct 2024
Cited by 7 | Viewed by 2674
Abstract
(1) Background: Methyl jasmonate-treated D. morbifera adventitious root extract (MeJA-DMARE), enriched with phenolics, has enhanced bioactivities. However, phenolics possess low stability and bioavailability. Substantial evidence indicates that plant extract–phospholipid complex assemblies, known as phytosomes, represent an innovative drug delivery system. (2) Methods: The [...] Read more.
(1) Background: Methyl jasmonate-treated D. morbifera adventitious root extract (MeJA-DMARE), enriched with phenolics, has enhanced bioactivities. However, phenolics possess low stability and bioavailability. Substantial evidence indicates that plant extract–phospholipid complex assemblies, known as phytosomes, represent an innovative drug delivery system. (2) Methods: The phytosome complex was created by combining MeJA-DMARE with Soy-L-α-phosphatidylcholine (PC) using three different ratios through two distinct methods (co-solvency method: A1, A2, and A3; thin-layer film method: B1, B2, and B3). (3) Results: Initial evaluation based on UV-Vis, entrapment efficiency (EE%), and loading content (LC%) indicated that B2 exhibited the highest EE% (79.98 ± 1.45) and LC% (69.17 ± 0.14). The phytosome displayed a spherical morphology with a particle size of 210 nm, a notably low polydispersity index of 0.16, and a superior zeta potential value at −25.19 mV. The synthesized phytosome exhibited superior anti-inflammatory activities by inhibiting NO and ROS production (reduced to 8.9% and 55.1% at 250 μg/mL) in RAW cells and adjusting the expression of related inflammatory cytokines; they also slowed lung tumor cell migration (only 2.3% of A549 cells migrated after treatment with phytosomes at 250 μg/mL), promoting ROS generation in A549 cell lines (123.7% compared to control) and stimulating apoptosis of lung cancer-related genes. (4) Conclusions: In conclusion, the MeJA-DMARE phytosome offers stable, economically efficient, and environmentally friendly nanoparticles with superior inflammation and lung tumor inhibition properties. Thus, the MeJA-DMARE phytosome holds promise as an applicable and favorable creation for drug delivery and lung cancer treatment. Full article
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26 pages, 5688 KB  
Article
Cordyceps militaris Grown on Germinated Rhynchosia nulubilis (GRC) Encapsulated in Chitosan Nanoparticle (GCN) Suppresses Particulate Matter (PM)-Induced Lung Inflammation in Mice
by Byung-Jin Park, Kyu-Ree Dhong and Hye-Jin Park
Int. J. Mol. Sci. 2024, 25(19), 10642; https://doi.org/10.3390/ijms251910642 - 3 Oct 2024
Cited by 6 | Viewed by 3617
Abstract
Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) exerts various biological effects, including anti-allergic, anti-inflammatory, and immune-regulatory effects. In this study, we investigated the anti-inflammatory effects of GRC encapsulated in chitosan nanoparticles (CN) against particulate matter (PM)-induced lung inflammation. Optimal CN (CN6) (CHI: [...] Read more.
Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) exerts various biological effects, including anti-allergic, anti-inflammatory, and immune-regulatory effects. In this study, we investigated the anti-inflammatory effects of GRC encapsulated in chitosan nanoparticles (CN) against particulate matter (PM)-induced lung inflammation. Optimal CN (CN6) (CHI: TPP w/w ratio of 4:1; TPP pH 2) exhibited a zeta potential of +22.77 mV, suitable for GRC encapsulation. At different GRC concentrations, higher levels (60 and 120 mg/mL) led to increased negative zeta potential, enhancing stability. The optimal GRC concentration for maximum entrapment (31.4 ± 1.35%) and loading efficiency (7.6 ± 0.33%) of GRC encapsulated in CN (GCN) was 8 mg/mL with a diameter of 146.1 ± 54 nm and zeta potential of +30.68. In vivo studies revealed that administering 300 mg/kg of GCN significantly decreased the infiltration of macrophages and T cells in the lung tissues of PM-treated mice, as shown by immunohistochemical analysis of CD4 and F4/80 markers. Additionally, GCN ameliorated PM-induced lung tissue damage, inflammatory cell infiltration, and alveolar septal hypertrophy. GCN also decreased total cells and neutrophils, showing notable anti-inflammatory effects in the bronchoalveolar lavage fluid (BALF) from PM-exposed mice, compared to GRC. Next the anti-inflammatory properties of GCN were further explored in PM- and LPS-exposed RAW264.7 cells; it significantly reduced PM- and LPS-induced cell death, NO production, and levels of inflammatory cytokine mRNAs (IL-1β, IL-6, and COX-2). GCN also suppressed NF-κB/MAPK signaling pathways by reducing levels of p-NF-κB, p-ERK, and p-c-Jun proteins, indicating its potential in managing PM-related inflammatory lung disease. Furthermore, GCN significantly reduced PM- and LPS-induced ROS production. The enhanced bioavailability of GRC components was demonstrated by an increase in fluorescence intensity in the intestinal absorption study using FITC-GCN. Our data indicated that GCN exhibited enhanced bioavailability and potent anti-inflammatory and antioxidant effects in cells and in vivo, making it a promising candidate for mitigating PM-induced lung inflammation and oxidative stress. Full article
(This article belongs to the Section Molecular Nanoscience)
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12 pages, 1579 KB  
Article
4-Hexylresorcinol Loaded Solid Lipid Nanoparticles for Enhancing Anticancer Activity
by Sooho Yeo, Sukkyun Jung, Haneul Kim, Jun-Hyun Ahn and Sung-Joo Hwang
Pharmaceuticals 2024, 17(10), 1296; https://doi.org/10.3390/ph17101296 - 29 Sep 2024
Cited by 8 | Viewed by 2488
Abstract
Background: Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery [...] Read more.
Background: Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery and cellular uptake of the drug. The purpose of this study is to encapsulate 4-HR into solid lipid nanoparticles (SLNs) to enhance its anti-cancer effect by avoiding aggregation and facilitating cellular uptake. Methods: 4-HR SLNs were prepared via hot melt homogenization with sonication. SLN characteristics were assessed by analyzing particle size, zeta potential, and drug release. Cytotoxicity, as an indicator of the anti-cancer effect, was evaluated against HeLa (cervical cancer in humans), A549 (lung cancer in humans), and CT-26 (colon carcinoma in mice) cell lines. Results: Particle size ranged from 169.4 to 644.8 nm, and zeta potential ranged from −19.8 to −40.3 mV, which are conducive to cellular uptake. Entrapment efficiency (EE) of 4-HR was found to be 75.0—96.5%. The cytotoxicity of 4-HR-loaded SLNs demonstrated enhanced anti-cancer effects compared to pure 4-HR. The enhancement of anti-cancer effects depended on reduced particle size based on cellular uptake, the EE, and the cell type. Conclusions: These findings imply that 4-HR-loaded SLN is a promising strategy for chemotherapy in cancer treatment. Full article
(This article belongs to the Special Issue Tumor Therapy and Drug Delivery)
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