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In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by par...
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... The lung presents several advantages as an application route, including its expansive surface area, thin alveolar epithelium, easily permeable membrane, and large vasculature. These characteristics enable the rapid and high absorption of soluble and permeable actives [40,41]. While some preclinical and clinical studies have been conducted in the literature on radiopharmaceuticals intended for SPECT imaging, there is currently no specific radiopharmaceutical established for lung cancer imaging in clinical practice [6]. ...
It is evident that radiolabeled drug delivery systems hold great promise in the field of lung cancer management. The combination of therapeutic agents with radiotracers not only allows for precise localization within lung tumors but also enables real-time monitoring of drug distribution. This approach has the potential to enhance targeted therapy and improve patient outcomes. The integration of advanced imaging modalities, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), has played a crucial role in the non-invasive tracking of radiolabeled drugs. These techniques provide valuable insights into drug pharmacokinetics, biodistribution, and tumor-targeting efficiency, offering clinicians the ability to personalize treatment regimens. The comprehensive analysis of preclinical and clinical studies presented in this review underscores the progress made in the field. The evidence suggests that radiolabeled drug delivery systems have the potential to revolutionize oncology by offering precise, targeted, and image-guided therapeutic interventions for lung cancer. This innovative approach not only enhances the effectiveness of treatment but also contributes to the development of personalized medicine strategies, tailoring interventions to the specific characteristics of each patient’s cancer. The ongoing research in this area holds promise for further advancements in lung cancer management, potentially leading to improved outcomes and quality of life for patients.
... Recently inhaled pulmonary drug delivery is preferred as it acts on target organs and has a systemic effect as well. Safe herbal inhalation therapy may be better due to its multi-targeted action and minimum adverse effects [7][8][9]. ...
While there are numerous published clinical trials investigating the efficacy of Ayurveda in managing bronchial asthma, a paucity of published case reports, case series, or randomized controlled trials (RCTs) concerning Basti (medicated enema) therapy in conjunction with Dhumapana (fumigation therapy) exists on PubMed.This scarcity of data hinders the comprehensive evaluation of this specific Ayurvedic approach for asthma management.
A 69-year-old female patient with a known case of bronchial asthma and hypertension presented with complaints of breathlessness on and off for 3 years, cough, urgency of micturition, constipation for 7 days, and fever for 3 days. The patient was treated according to the treatment principles of Tamakshwas (bronchial asthma) and Jwara (fever). Basti, Dhumapana, and oral Ayurvedic formulations were administered. Significant improvements in symptoms, the mMRC dyspnea scale, and the pulmonary function test were observed.
This case provides new insight into clinical diagnosis and management through gut modulation in respiratory diseases and vice versa.
... Drug delivery via inhalation is a promising and noninvasive administration for respiratory disease [40,41]. However, inhalation delivery commonly requires aerosolization, propelled by mechanical vibration and pressurization, which is a well-identified physical stress to large protein molecules. ...
... This molecule confers potent and broad neutralization against SARS-CoV-2 viral variants and selected animal CoVs and provides protection against SARS-CoV-2 challenge in mice. Inhalation delivery can directly deposit the decameric ACE2 to the mucosal site [40,41], effectively blocking SARS-CoV-2 replication and further evolution, and potentially reducing its transmission at population levels. The molecule has shown robust biochemical and biophysical profiles suitable for further development as an aerosolized antiviral agent. ...
The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.
... Protein absorption by inhalation is limited by anatomical, physiological and immunological barriers. 43 Due to the extensive branching structure of the airways, the aerodynamic particle properties determine how far drugs can attain; only particles or droplets with an appropriate aerodynamic diameter (between ca. 1 and 5 mm) may reach the lungs via inhalation. Mucociliary clearance, pulmonary surfactant, airway epithelium and macrophages and other inflammatory cells are further barriers that protect the airways from foreign substances. ...
... ○ Dermal bioavailability is negligible due to high molecular weight and hydrophilic character which makes transdermal absorption unlikely 38 ○ Oral bioavailability is negligible from degradation in the GI tract due to enzymatic activity, low pH and intestinal barriers 39,40 ○ Inhalation bioavailability for mAbs is <5 % due to negligible aerosolization potential, airway structure, mucociliary clearance, pulmonary surfactant, macrophages, and other inflammatory cells 36,37,43,47,48 Drug generally handled in diluted state in final dosage form (solution) 54 Drug product is rapidly degraded leading to negligible exposure risk from surface contamination 9 Healthcare facilities routinely use engineering controls (e.g., ventilated enclosures) and personal protective equipment Routine work practices are not associated with significant exposures CSTDs have little to no evidence of additional protection even for small molecules 55 ...
... Consequently, there has been much research into alternative, less invasive delivery routes. Some progress has been made in this regard, with the pulmonary [2] and nasally [3] delivered biologics already on the market, and research ongoing into other mucosal delivery options [4]. The transdermal route is an attractive choice for drug administration, being convenient and well-accepted by patients. ...
Despite much research over the last few decades, microneedle arrays for the transdermal delivery of drugs have failed to live up to their initial promise. This may be changing however as companies close in on the commercial delivery of vaccines via this technology. These breakthroughs will undoubtably increase the interest in the use of microneedles arrays for the delivery of biopharmaceuticals but will also drive research into the development of scalable manufacturing processes for their fabrication. While 3D printing is an exciting development in this field, conventional Additive Manufacturing (AM) techniques are unsuitable for biopharmaceuticals due to the harsh processing conditions which can cause degradation of the active ingredient. In this paper we report the first use of Aerosol Jet Printing (AJP) as an AM technique for the fabrication of dissolving microneedle arrays. A formulation of poly(vinyl pyrrolidone), trehalose and glycerol dissolved in water was prepared and characterised. The formulation was aerosolised using ultrasonication and deposited onto a silicon substrate. Critical process parameters such as Computer Aided Design (CAD) design, flow rate, temperature , print speed and focussing ratio were studied to determine their impact on the microneedle quality attributes. 4 × 4 microneedle arrays were printed, with needle heights > 500 µm achieved with print times of 30 mins or less. The resulting needles had sufficient strength and sharpness to penetrate porcine skin samples. Importantly, the microneedles can be fabricated under benign conditions which should be suitable for the processing and subsequent delivery of biopharmaceuticals across the skin.
... Due to the high permeability of the lung tissue due to its type of tissue structure, it will lead to rapid absorption and, as a result, the rapid onset of the medicinal effect [56]. According to the studies, it has been shown that the pulmonary epithelial barrier is relatively permeable for macromolecules [57]. ...
... According to the studies, it has been shown that the pulmonary epithelial barrier is relatively permeable for macromolecules [57]. Many anatomical, physiological and immunological factors and barriers, including mucociliary clearance, surfactants in the lung, the permeability of the pulmonary epithelium, enzymatic metabolism and the branched structure of the airways can affect the transfer of protein drugs and peptides [56]. ...
Abstract
As bioactive molecules, peptides and proteins are essential in living organisms, including animals and humans. Defects in their function lead to various diseases in humans. Therefore, the use of proteins in treating multiple diseases, such as cancers and hepatitis, is increasing. There are different routes to administer proteins, which have limitations due to their large and hydrophilic structure. Another limitation is the presence of biological and lipophilic membranes that do not allow proteins to pass quickly. There are different strategies to increase the absorption of proteins from these biological membranes. One of these strategies is to use compounds as absorption enhancers. Absorption enhancers are compounds such as surfactants, phospholipids, and cyclodextrins that increase protein passage through the biological membrane and their absorption by different mechanisms. This review focuses on using other absorption enhancers and their mechanism in protein administration routes.
... Therapeutic proteins include molecules ranging in size from 1 to 50 kDa to much larger proteins like monoclonal antibodies (mAbs) with around 150 kDa; thus, even the smallest of these molecules exceed in size the so-called conventional drugs, such as aspirin ( Figure 1) [23][24][25]. ...
... Therapeutic proteins include molecules ranging in size from 1 to 50 kDa to much larger proteins like monoclonal antibodies (mAbs) with around 150 kDa; thus, even the smallest of these molecules exceed in size the so-called conventional drugs, such as aspirin ( Figure 1) [23][24][25]. The higher molecular weight of peptides and proteins impedes them from crossing the intestine mucosa [26] and other membranes. ...
... However, some factors affect the delivery efficacy of inhaled proteins and peptides, with the primary barrier for inhaled particle deposition being the highly branching structure of the lung [23]. The rate and extent of this process depend significantly on the physicochemical properties of aerosol particles, especially the diameter of a particle in airflow, referred to as aerodynamic diameter [56,58]. ...
Proteins and peptides are potential therapeutic agents, but their physiochemical properties make their use as drug substances challenging. Hydrogels are hydrophilic polymeric networks that can swell and retain high amounts of water or biological fluids without being dissolved. Due to their biocompatibility, their porous structure, which enables the transport of various peptides and proteins, and their protective effect against degradation, hydrogels have gained prominence as ideal carriers for these molecules’ delivery. Particularly, stimuli-responsive hydrogels exhibit physicochemical transitions in response to subtle modifications in the surrounding environment, leading to the controlled release of entrapped proteins or peptides. This review is focused on the application of these hydrogels in protein and peptide delivery, including a brief overview of therapeutic proteins and types of stimuli-responsive polymers.
... Therefore, a more significant proportion of Pb is absorbed by the lungs. 33 Nemmar et al. previously reported that ultrafine particles (<100 nm) can be directly absorbed. 34 In contrast, poorly soluble Pb mass can be chronically deposited in the lung. ...
Lead-based perovskite nanoparticles (Pb-PNPs) have found extensive applications across diverse fields. However, because of poor stability and relatively strong water solubility, the potential toxicity of Pb-PNPs released into the environment during their manufacture, usage, and disposal has attracted significant attention. Inhalation is a primary route through which human exposure to Pb-PNPs occurs. Herein, the toxic effects and underlying molecular mechanisms of Pb-PNPs in the respiratory system are investigated. The in vitro cytotoxicity of CsPbBr3 nanoparticles in BEAS-2B cells is studied using multiple bioassays and electron microscopy. CsPbBr3 nanoparticles of different concentrations induce excessive oxidative stress and cell apoptosis. Furthermore, CsPbBr3 nanoparticles specifically recruit the TGF-β1, which subsequently induces epithelial-mesenchymal transition. In addition, the biodistribution and lung toxicity of representative CsPbBr3 nanoparticles in ICR mice are investigated following intranasal administration. These findings indicate that CsPbBr3 nanoparticles significantly induce pulmonary inflammation and epithelial-mesenchymal transition and can even lead to pulmonary fibrosis in mouse models. Above findings expose the adverse effects and molecular mechanisms of Pb-PNPs in the lung, which broadens the safety data of Pb-PNPs.
... 24 Finally, metered-dose inhalers (MDIs) create fixed-dose aerosols 25 but come with the limitation of requiring lipophilic propellers, which hydrophilic biologics cannot solve, 26 thus limiting their dose range. 27,28 Search strategy On June 20, 2023, we searched PubMed for English-language literature published after December 1, 2019, using the query "SARS-CoV-2 AND (intranasal OR nasal OR inhaled OR aerosol OR spray OR inhalable) AND ("monoclonal antibody" OR "convalescent plasma" or "immunoglobulins" or "nanobodies" or "scFv")." ...
Convalescent plasma has been extensively tested during the COVID-19 pandemic as a transfusion product. Similarly, monoclonal antibodies have been largely administered either intravenously or intramuscularly. Nevertheless, when used against a respiratory pathogen, respiratory delivery is preferable to maximize the amount of antibody that reaches the entry door in order to prevent sustained viral multiplication. In this narrative review, we review the different types of inhalation device and summarize evidence from animal models and early clinical trials supporting the respiratory delivery (for either prophylactic or therapeutic purposes) of convalescent plasma or monoclonal antibodies (either full antibodies, single-chain variable fragments, or camelid-derived monoclonal heavy-chain only antibodies). Preliminary evidences from animal models suggest similar safety and noninferior efficacy, but efficacy evaluation from clinical trials is still limited.
... Drug delivery via inhalation is a promising and noninvasive administration for respiratory disease [40,41]. However, inhalation delivery commonly requires aerosolization, propelled by mechanical vibration and pressurization, which is a well-identified physical stress to large protein molecules. ...
... This molecule confers potent and broad neutralization against SARS-CoV-2 viral variants and selected animal CoVs and provides protection against SARS-CoV-2 challenge in mice. Inhalation delivery can directly deposit the decameric ACE2 to the mucosal site [40,41], effectively blocking SARS-CoV-2 replication and further evolution, and potentially reducing its transmission at population levels. The molecule has shown robust biochemical and biophysical profiles suitable for further development as an aerosolized antiviral agent. ...
The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.
