Cromoglycate Research Articles

Influence of microbubbles on the production of spray-dried inhalable particles

The aim of this work was to study the effect of gas microbubbles on the production of particles suitable for inhalatory administration by a spray drying technology. An antiasthmatic model drug (sodium cromoglycate) was selected in order to evaluate the effect of different gases (air, CO2 and N2) and spray drying operating conditions on the particles aerosolization performance. To this end, gas supersaturated aqueous drug solutions were obtained in a pressurized vessel and then processed by spray drying. The process yield, morphology, size, bulk and tap densities, moisture content and aerosolization properties of the particles were evaluated. The presence of microbubbles in the spray drying feed led to powders with smaller mean geometric sizes than particles obtained without bubbles. The gas-water solubility emerged as a key parameter to obtain inhalatory particles with good aerosolization properties. High water-soluble gases led to bigger particles, while low soluble ones allow to produce smaller particles. The use of air (with an intermediate water solubility respect to CO2 and N2) and an adequate set of spray drying operating conditions allowed to obtain sodium cromoglycate particles with superior aerosolization properties than a commercial formulation. Overall, a novel, simple and low-cost method to produce inhalatory particles with excellent aerosolization properties was developed by supersaturating the spray drying liquid feed without using pore-forming agents during the production step, or carriers in the final formulation.

Mast cells in the paraventricular nucleus participate in visceral hypersensitivity induced by neonatal maternal separation

Early-life stress (ELS) is a high-risk factor for the development of chronic visceral pain in adulthood. Emerging evidence suggests that mast cells play a key role in the development of visceral hypersensitivity through interaction with neurons. The sensitization of corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) plays a pivotal role in the pathogenesis of visceral pain. However, the precise mechanism by which mast cells and CRF neurons interact in the PVN in the pathogenesis of visceral hypersensitivity remains elusive. In the present study, we used neonatal maternal separation (MS), an ELS model, and observed that neonatal MS induced visceral hypersensitivity and triggered PVN mast cell activation in adult rats, which was repressed by intra-PVN infusion of the mast cell stabilizer disodium cromoglycate (cromolyn). Wild-type (WT) mice but not mast cell-deficient KitW-sh/W-sh mice that had experienced neonatal MS exhibited chronic visceral hypersensitivity. MS was associated with an increase in the expression of proinflammatory mediators, the number of CRF+ cells and CRF protein in the PVN, which was prevented by intra-PVN infusion of cromolyn. Furthermore, we demonstrated that intra-PVN infusion of the mast degranulator compound 48/80 significantly induced mast cell activation, resulting in proinflammatory mediator release, CRF neuronal sensitization, and visceral hypersensitivity, which was suppressed by cromolyn. Overall, our findings demonstrated that neonatal MS induces the activation of PVN mast cells, which secrete numerous proinflammatory mediators that may participate in neighboring CRF neuronal activity, ultimately directly inducing visceral hypersensitivity in adulthood.

Inhibitory effect of desflurane on degranulation of mast cells induced by lateral ventricular injection of stimulator-C48/80 in C57BL/6 male mice

Inhalation of anesthetic agents have been observed to confer neuroprotection for decades. The present study was intended to determine whether desflurane (DES) prohibits mast cells (MCs) from degranulation induced by lateral ventricular injection (LVC) with Compound 48/80 (C48/80) in C57BL/6. Total 100 mice were recruited to this study, but only 88 male mice (20–24 weeks) were survived from the procedure, and randomized and allocated into four groups: (A) the saline group; (B) the C48/80 group; (C) the sodium cromoglycate (CRO + C48/80) group; (D) 7.5% DES preconditioning for 2 h + C48/80 lateral ventricular injection (DES + C48/80) group. The slices of mice brain thalamus were performed for toluidine blue staining (MCs) and immunochemistry (fluorescence of Iba1 and GFAP, respectively), and brain tissues were extracted to probe IL-6, TNF-α, NF-κB (p65), and TLR4 against GAPDH by western blotting. Our results demonstrated that administration of C48/80 provoked degranulation of mast cells at thalamus, increasing the fluorescence intensities of Iba1 and GFAP, and over-expressing IL-6, TNF-α, NF-κB(p65), and TLR4. However, pre-conditioning inhalation of DES prohibited MCs from degranulation, diminishing the fluorescent intensities of Iba1 and GFAP, decreasing expressed levels of IL-6, TNF-α, NF-κB(p65), as well as TLR4. It suggests inhalation DES could inhibit the neuroinflammation and deactivate glial and astrocytes via direct prohibiting degranulation of MCs at thalamus in the central nervous system (CNS).

Re-Profiling of US-FDA Approved Drugs for COVID-19 by In-silico Studies

Covid-19 is an infectious disease that has rattled the world. Although several new vaccines are being administered to prevent infections, there is a large unmet need for antiviral drugs to ameliorate disease progression. In this study, structures of endogenous proteins were modelled using the genome browser and screened for molecular docking of drugs with spike protein of SARS COV-2 binding to ACE2 receptor using bioinformatics approaches such as structure-assisted drug design (SBDD), virtual drug screening (VS), and high-throughput screening (HTS). We have screened 150 drugs that were shortlisted from extensive literature data, 110 of these have been approved by the US-FDA for various diseases. We have developed a molecule assessment process from which we have identified fifteen drugs that have the potential for repurposing towards blocking SARS-COV2 proteins with endogenous proteins. Using these approaches, we have identified asthma drugs such as Cromolyn sodium, Ciclesonide and Zafirlukast.

Sculpting the shapes of giant unilamellar vesicles using isotropic-nematic-isotropic phase cycles.

Understanding how soft matter deforms in response to mechanical interactions is central to the design of functional synthetic materials as well as elucidation of the behaviors of biological assemblies. Here we explore how cycles of thermally induced transitions between nematic (N) and isotropic (I) phases can be used to exert cyclical elastic stresses on dispersions of giant unilamellar vesicles (GUVs) and thereby evolve GUV shape and properties. The measurements were enabled by the finding that I-N-I phase transitions of the lyotropic chromonic liquid crystal disodium cromoglycate, when conducted via an intermediate columnar (M) phase, minimized transport of GUVs on phase fronts to confining surfaces. Whereas I to N phase transitions strained spherical GUVs into spindle-like shapes, with an efflux of GUV internal volume, subsequent N to I transitions generated a range of complex GUV shapes, including stomatocyte, pear- and dumbbell-like shapes that depended on the extent of strain in the N phase. The highest strained GUVs were observed to form buds (daughter vesicles) that we show, via a cycle of I-N-I-N phase transitions, are connected via a neck to the parent vesicle. Additional experiments established that changes in elasticity of the phase surrounding the GUVs and not thermal expansion of membranes were responsible for the shape transitions, and that I-N-I transformations that generate stomatocytes can be understood from the Bilayer-Coupling model of GUV shapes. Overall, these observations advance our understanding of how LC elastic stresses can be regulated to evolve the shapes of soft biological assemblies as well as provide new approaches for engineering synthetic soft matter.

Time Dependent Lyotropic Chromonic Textures in Microfluidic Confinements

Nematic and columnar phases of lyotropic chromonic liquid crystals (LCLCs) have been long studied for their fundamental and applied prospects in material science and medical diagnostics. LCLC phases represent different self-assembled states of disc-shaped molecules, held together by noncovalent interactions that lead to highly sensitive concentration and temperature dependent properties. Yet, microscale insights into confined LCLCs, specifically in the context of confinement geometry and surface properties, are lacking. Here, we report the emergence of time dependent textures in static disodium cromoglycate (DSCG) solutions, confined in PDMS-based microfluidic devices. We use a combination of soft lithography, surface characterization, and polarized optical imaging to generate and analyze the confinement-induced LCLC textures and demonstrate that over time, herringbone and spherulite textures emerge due to spontaneous nematic (N) to columnar M-phase transition, propagating from the LCLC-PDMS interface into the LCLC bulk. By varying the confinement geometry, anchoring conditions, and the initial DSCG concentration, we can systematically tune the temporal dynamics of the N- to M-phase transition and textural behavior of the confined LCLC. Overall, the time taken to change from nematic to the characteristic M-phase textures decreased as the confinement aspect ratio (width/depth) increased. For a given aspect ratio, the transition to the M-phase was generally faster in degenerate planar confinements, relative to the transition in homeotropic confinements. Since the static molecular states register the initial conditions for LC flows, the time dependent textures reported here suggest that the surface and confinement effects—even under static conditions—could be central in understanding the flow behavior of LCLCs and the associated transport properties of this versatile material.

Development of Advanced Chemometric-Assisted Spectrophotometric Methods for the Determination of Cromolyn Sodium and Its Alkaline Degradation Products.

Advanced and sensitive spectrophotometric and chemometric analytical methods were successfully established for the stability-indicating assay of cromolyn sodium (CS) and its alkaline degradation products (Deg1 and Deg2). Spectrophotometric mean centering ratio spectra method (MCR) and chemometric methods, including principal component regression (PCR) and partial least square (PLS-2) methods, were applied. Peak amplitudes after MCR at 367.8 nm, 373.8 nm and 310.6 nm were used within linear concentration ranges of 2–40 µg mL−1, 5–40 µg mL−1 and 10–100 µg mL−1 for CS, Deg1 and Deg2, respectively. For PCR and PLS-2 models, a calibration set of eighteen mixtures and a validation set of seven mixtures were built for the simultaneous determination of CS, Deg1 and Deg2 in the ranges of 5–13 µg mL−1, 8–16 µg mL−1, and 10–30 µg mL−1, respectively. The authors emphasize the importance of a stability-indicating strategy for the investigation of pharmaceutical products.

Beclomethasone dipropionate and sodium cromoglycate protect against airway hyperresponsiveness in a human ex vivo model of cow's milk aspiration

BackgroundRecurrent cow's milk (CM) aspiration is often associated with gastroesophageal reflux in infants and toddlers and it seems to be implicated in the etiology of different inflammatory lung disorders. This study aimed to investigate ex vivo the impact of CM aspiration on human airways and whether treatment with beclomethasone dipropionate (BDP) or sodium cromoglycate (SCG) may prevent the potential CM-induced airway hyperresponsiveness (AHR). MethodsHuman isolated bronchi were contracted by electrical field stimulation (EFS10Hz) to mimic the contractile tone induced by the parasympathetic activity and challenged with CM, fat/lactose-free CM, or human breast milk (HM). The effect of pre-treatment with beclomethasone dipropionate (BDP) and sodium cromoglycate (SCG) was also investigated on the AHR induced by CM. ResultsAfter a 60 min-challenge with CM 1:10 v/v and fat/lactose-free CM 1:10 v/v, ASM significantly (P ​< ​0.05) increased compared to control (+67.04 ​± ​17.08% and +77.91 ​± ​1.34%, respectively), a condition that remained stable for 150 ​min post-treatment, whereas HM did not alter ASM contractility. BDP 1 ​μM and 10 ​μM significantly (P ​< ​0.05) reduced the AHR elicited by CM (−52.49 ​± ​10.97% and −66.98 ​± ​7.90%, respectively vs. control). At the same manner, SCG 1 ​μM and 10 ​μM significantly (P ​< ​0.05) inhibited the CM-induced AHR (−59.03 ​± ​9.24% and −73.52 ​± ​7.41%, respectively vs. control). ConclusionCM induces AHR in human ASM by eliciting an increased parasympathetic contractile response. Preventive treatment with nebulized SCG may be indicated in infants or toddlers fed with CM, rather than with BDP due to a superior safety profile.

The role of mast cells, C-fibers, and cholinergic transmission in the reduction of tracheal muscle and mronchi of sensitized animal

The article considers the role of stabilization of mast cell membranes, blockade of neuromuscular transmission and inactivation of C-fibers in the contractile activity of smooth muscles of the trachea and bronchi of sensitized rats. The studies were conducted on isolated preparations using electrical stimulation of postganglionic nerves (frequency - 30 stim/s, duration - 0.5 ms, amplitude - 20 V, duration of stimulation - 10 s). The study used cromolyn sodium, atropine, and capsaicin. As a result of the experiments, it was found that the leading role in the contraction of the muscles of the trachea and bronchi of a sensitized rat belongs to mast cells. However, the maximum effect of normalization of smooth muscle contraction can be achieved only in the case of a complex effect - blockade of neuromuscular transmission, stabilization of mast cell membranes, and inactivation of C-fibers.

Dynamic guiding of bacteria in lyotropic chromonic liquid crystal using magnetic field

This article demonstrates a new approach enabling the active control of swimming trajectories of flagellated bacteria in space and time. Bacteria were mixed with water solutions of disodium cromoglycate (DSCG), a lyotropic chromonic liquid crystal (LCLC) that mimics the anisotropic properties of many biological environments. It has been well established that the bacteria then swim in the direction of the self-aligned molecular aggregates of DSCG. It is also known that this host material possesses a diamagnetic anisotropy enabling the control of the local orientation of these aggregates with magnetic fields (MF). This double coupling (bacteria-LCLC & LCLC-MF) allows the efficient real-time control of the orientation of bacterial trajectories. Such control over the motility of microorganisms opens numerous avenues for their manipulation and study, for example, in a lab-on-a-chip device.

Thermal degradation and drug sorption in hybrid interpolyelectrolyte particles

Magnetic compounds, based on magnetite nanoparticles and interpolyelectrolyte complexes (IPEC) were prepared from chitosan (CS) and poly(sodium 4-styrenesulfate) (NaPSS). Two types of composite were obtained: one with positive surface charge and another one with negatively charged surface. The composites were used to adsorb a cationic drug (tetracycline hydrochloride, HTCCl) and an anionic one (sodium cromoglycate, NaCG). Sorption occurred in the form of multiple layers, tending to a saturation value (following Sips isotherm), with saturation sorption concentrations of ca. 0.2 mmol of drug per gram of composite for HTCCl on both positively and negatively charged composites, probably due to the protonation of chitosan by HTCCl. In the case of the anionic drug, it was adsorbed with the same intensity on the composite of opposite charge, while for the composite with negative charge saturation occurred at a value of ca. 0.05 mol per gram of composite. Gibbs free energy of adsorption for dilute solution conditions was estimated, ranging from ‒17 to −3 kJ/mol, and the analysis of thermal degradation kinetics of composites, using the isoconversional approach, indicated that magnetite decreased apparent energy of activation (with values reaching 400 kJ/mol) for the degradation of the organic phase.

Design of Potential Pharmaceutical-Based Metal Complexes Derived from Cromolyn a Mast Cell Stabilizer.

A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca, were formed through reactions under controlled temperature and pH conditions. Additional characterization for these materials was performed employing a number of solid-state characterization techniques, such as thermogravimetric analysis (TGA), powder and single-crystal X-ray diffraction (PXRD and SCXRD), and scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS). TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies, while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only two-dimensional (2D) structures were achieved under the conditions studied. These binding modalities might affect the activity and delivery of cromolyn sodium (CS). The stability of the metal complexes was assessed in phosphate-buffered saline (PBS, pH = 7.40) and fasted-state simulated gastric fluids (FaSSGF, pH = 1.60). Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37 °C.

Pioneer Part 2: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib in Indolent Systemic Mastocytosis

Pioneer Part 2: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib in Indolent Systemic Mastocytosis

No dose effect observed with chronic fluticasone propionate on growth velocity in children

Inhaled corticosteroid (ICS) therapy is recommended for most children with asthma irrespective of severity. Although this risks growth suppression, the benefit/risk profile is considered favorable.1,2 The effects of ICS on growth have mainly been evaluated in placebo-controlled trials; other controls used include nedocromil, montelukast, and sodium cromoglicate. Given the established role of ICS in treating asthma, it would not be ethical to enroll patients with moderate-severe asthma into a study where they may be randomized to non-ICS therapy. Therefore, much of the data characterizing the growth-suppressive effects of ICS comes from children with mild-moderate asthma.

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

DNA Origami Nano-Sheets and Nano-Rods Alter the Orientational Order in a Lyotropic Chromonic Liquid Crystal.

Rod-like and sheet-like nano-particles made of desoxyribonucleic acid (DNA) fabricated by the DNA origami method (base sequence-controlled self-organized folding of DNA) are dispersed in a lyotropic chromonic liquid crystal made of an aqueous solution of disodium cromoglycate. The respective liquid crystalline nanodispersions are doped with a dichroic fluorescent dye and their orientational order parameter is studied by means of polarized fluorescence spectroscopy. The presence of the nano-particles is found to slightly reduce the orientational order parameter of the nematic mesophase. Nano-rods with a large length/width ratio tend to preserve the orientational order, while more compact stiff nano-rods and especially nano-sheets reduce the order parameter to a larger extent. In spite of the difference between the sizes of the DNA nano-particles and the rod-like columnar aggregates forming the liquid crystal, a similarity between the shapes of the former and the latter seems to be better compatible with the orientational order of the liquid crystal.

Mast Cell Deficiency Protects Mice from Surgery-Induced Neuroinflammation.

Neuroinflammation plays a key role in the occurrence and development of neurodegenerative diseases. Microglia, the resident immune cells in the brain, have been recognized to contribute to neuroinflammation. Previous studies have shown that activated mast cells may be involved in surgery-induced neuroinflammation and neuronal apoptosis by using pharmacological methods. This study is aimed at ascertaining the exactly role of mast cells on neuroinflammation with the mast cell-deficient mice. Adult male C57BL6/J wild-type (WT) and mast cell-deficient (C57BL6/J KitWsh/Wsh (Wsh)) mice underwent tibial fracture surgery. Blood-brain barrier (BBB) breakdown, microglial activation, and neuroinflammatory levels were examined at 1 day after surgery. Surgery-induced BBB breakdown, microglial activation, and neuroinflammatory levels were significantly, pharmacologically reduced using a mast cell stabilizer, cromolyn sodium in WT mice (P < 0.05). These results were reproduced with mast cell deficiency. WT mice administered intraventricularly with cromolyn exhibited reduced BBB breakdown, microglial activation, and neuroinflammatory levels versus vehicle (P < 0.05). But there was no effect of cromolyn versus vehicle in Wsh mice, clarifying the specificity of cromolyn on brain mast cells. These findings demonstrated that activated mast cells promote surgery-induced BBB breakdown and neuroinflammation in mice, and open up a new therapeutic target for neuroinflammation-related diseases.

Sodium Cromoglycate Decreases Sensorimotor Impairment and Hippocampal Alterations Induced by Severe Traumatic Brain Injury in Rats.

Severe traumatic brain injury (TBI) results in significant functional disturbances in the hippocampus. Studies support that sodium cromoglycate (CG) induces neuroprotective effects. This study focused on investigating the effects of post-TBI subchronic administration of CG on hippocampal hyperexcitability and damage as well as on sensorimotor impairment in rats. In contrast to the control group (Sham+SS group), animals undergoing severe TBI (TBI+SS group) showed sensorimotor dysfunction over the experimental post-TBI period (day 2, 55%, p < 0.001; day 23, 39.5%, p < 0.001; day 30, 38.6%, p < 0.01). On day 30 post-TBI, TBI+SS group showed neuronal hyperexcitability (63.3%, p < 0.01). The hippocampus ipsilateral to the injury showed volume reduction (14.4%, p < 0.001) with a volume of damage of 0.15 ± 0.09 mm3. These changes were associated with neuronal loss in the dentate gyrus (ipsilateral, 33%, p < 0.05); hilus (ipsilateral, 77%, p < 0.001; contralateral, 51%, p < 0.001); Cornu Ammonis (CA)1 (ipsilateral, 40%, p < 0.01), and CA3 (ipsilateral, 52%, p < 0.001; contralateral, 34%, p < 0.01). Animals receiving subchronic treatment with CG (50 mg/kg, s.c. daily for 10 days) after TBI (TBI+CG group) displayed a sensorimotor dysfunction less evident than that of the TBI+SS group (p < 0.001). Their hippocampal excitability was similar to that of the Sham+SS group (p = 0.21). The TBI+CG group presented hippocampal volume reduction (12.7%, p = 0.94) and damage (0.10 ± 0.03 mm3, p > 0.99) similar to the TBI+SS group. However, their hippocampal neuronal preservation was similar to that of the Sham+SS group. These results indicate that CG represents an appropriate and novel pharmacological strategy to reduce the long-term sensorimotor impairment and hippocampal damage and hyperexcitability that result as consequences of severe TBI.

Natural α,β-unsaturated lactones inhibit neuropeptide-induced mast cell activation in an in vitro model of neurogenic inflammation.

Mast cells are involved in not only inducing, but also maintaining neurogenic inflammation and neuropathic pain. In previous work, we have demonstrated that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit rat peritoneal and human LAD2 mast cell degranulation induced by compound 48/80 and calcium ionophore A23187. However, the effect of these molecules on neuropeptide-induced mast cell activation has not been studied so far. The aim of this study was to determine whether dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one inhibit neuropeptide-induced mast cell activation. This work is based on in vitro simulation of a neurogenic inflammation scenario involving neuropeptides and mast cells, to subsequently analyze potential therapeutic strategies for neuropathic pain. Neuromedin-N did not stimulate mast cell serotonin release but substance P and neurotensin did induce serotonin release from peritoneal mast cells in a dose-dependent manner. Mast cell serotonin release induced by substance P and neurotensin was inhibited by dehydroleucodine and xanthatin, but not by 3-benzyloxymethyl-5H-furan-2-one. The inhibitory potency of dehydroleucodine and xanthatin was higher than that obtained with the reference compounds, ketotifen and sodium chromoglycate, when mast cells were preincubated with dehydroleucodine before substance P incubation, and with dehydroleucodine or xanthatin before neurotensin incubation. These results are the first strong evidence supporting the hypothesis that dehydroleucodine and xanthatin inhibit substance P- and neurotensin-induced serotonin release from rat peritoneal mast cells. Our findings suggest, additionally, that these α,β-unsaturated lactones could be of value in future pharmacological research related to inappropriate mast cell activation conditions such as neurogenic inflammation and neuropathic pain.

Hydrophobic ion pair loaded self-emulsifying drug delivery system (SEDDS): A novel oral drug delivery approach of cromolyn sodium for management of bronchial asthma.

The aim of the present study is to develop a self-emulsifying drug delivery system (SEDDS) for the hydrophobic ion pair (HIP) complex of cromolyn sodium (CS), in order to enhance its intestinal absorption and biological activity. Two ion pairing agents (IPAs) were investigated: hexadecyl pyridininum chloride (HPC) and myristyl trimethyl ammonium bromide (MTAB). The optimum binding efficiency for complexation between investigated IPAs and CS was observed at a molar ratio of 1.5:1, where CS binding efficiency was found to be 76.10±2.12 and 91.37±1.73% for MTAB and HPC, respectively. The two prepared complexes exhibited a significant increase in partition coefficient indicating increased lipophilicity. The optimized CS-HIP complex was incorporated into SEDDS formulations. SEDDS formulations F2 (40% oleic acid, 40% BrijTM98, 20% propylene glycol) and F3 (25% oleic acid, 50% BrijTM98, 25% propylene glycol) exhibited nanometric droplet diameters with monodisperse distribution and nearly neutral zeta potential values. Ex vivo intestinal permeation study, using the non-everted gut sac technique, revealed a significantly higher cumulative amount of permeated drug, after 2h, for F2 and F3 (53.836 and 77.617µg/cm2, respectively) compared to 8.649µg/cm2 for plain CS solution. The in vivo evaluation of plain CS solution compared to F2 and F3 was conducted in an ovalbumin sensitization-induced bronchial asthma rat model. Lung function parameters (tidal volume and peak expiratory flow), biochemical parameters (interleukin-5, immunoglobulin-E, myeloperoxidase and airway remodelling parameters) were assessed in addition to histopathological examination. The results indicated the superiority of F3 followed by F2 compared to plain CS solution for prophylaxis of bronchial asthma in rats.