Chemotherapeutic drug targeting to lungs by way of microspheres after intravenous administration

Sangi, Sibghatullah; Sreeharsha, Nagaraja; Bawadekji, Abdulhakim; Ali, Mouhanad Al

doi:10.2147/dddt.s173485

Cited by 14 publications

(6 citation statements)

References 30 publications

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“…Additionally, a trend can be seen where an increase in voltage leads to a decrease in uniformity ( Figure 1 ). An increase in spray voltage leads to a rise in the repulsive force between droplets due to ion movement towards the droplet surface, leading to the instability of the jet at high voltages [ 35 ]. As shown in Figure 1 , to achieve the best uniformity, a lower flow rate and voltage should be chosen.…”

Section: Resultsmentioning

confidence: 99%

Design of Pectin-Based Hydrogel Microspheres for Targeted Pulmonary Delivery

Chai,

Schmidt,

Brewster

et al. 2023

Gels

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Pulmonary drug delivery via microspheres has gained growing interest as a noninvasive method for therapy. However, drug delivery through the lungs via inhalation faces great challenges due to the natural defense mechanisms of the respiratory tract, such as the removal or deactivation of drugs. This study aims to develop a natural polymer-based microsphere system with a diameter of around 3 μm for encapsulating pulmonary drugs and facilitating their delivery to the deep lungs. Pectin was chosen as the foundational material due to its biocompatibility and degradability in physiological environments. Electrospray was used to produce the pectin-based hydrogel microspheres, and Design-Expert software was used to optimize the production process for microsphere size and uniformity. The optimized conditions were determined to be as follows: pectin/PEO ratio of 3:1, voltage of 14.4 kV, distance of 18.2 cm, and flow rate of 0.95 mL/h. The stability and responsiveness of the pectin-based hydrogel microspheres can be altered through coatings such as gelatin. Furthermore, the potential of the microspheres for pulmonary drug delivery (i.e., their responsiveness to the deep lung environment) was investigated. Successfully coated microspheres with 0.75% gelatin in 0.3 M mannitol exhibited improved stability while retaining high responsiveness in the simulated lung fluid (Gamble’s solution). A gelatin-coated pectin-based microsphere system was developed, which could potentially be used for targeted drug delivery to reach the deep lungs and rapid release of the drug.

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Section: Resultsmentioning

confidence: 99%

Design of Pectin-Based Hydrogel Microspheres for Targeted Pulmonary Delivery

Chai,

Schmidt,

Brewster

et al. 2023

Gels

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“…The particle size of the microspheres is the main important factor as it controls the tissue location of the microspheres after intravenous administration. Previous reports have proved that microspheres with the size range of 5–25 μm have a notable lung targeting due to mechanical trapping in the fine blood capillaries of the lung [ 17 , 19 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast to nanoparticles, microspheres offer a well-established platform technology for easy commercialization and effective delivery by oral, parenteral as well as nasal routes [15,16]. The methodology applies to a wide range of therapeutics with diverse physicochemical properties like small antibiotic molecules and peptides, and proteins [17]. Huo et al [18] showed that cisplatin-loaded biodegradable PLGA microspheres could achieve successful accumulation of particles in lungs after parenteral administration along with a sustained release for effective long-term therapy to reduce the frequency of dosing.…”

Section: Introductionmentioning

confidence: 99%

Lung Targeted Lipopolymeric Microspheres of Dexamethasone for the Treatment of ARDS

et al. 2021

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Acute respiratory distress syndrome (ARDS), a catastrophic illness of multifactorial etiology, involves a rapid upsurge in inflammatory cytokines that leads to hypoxemic respiratory failure. Dexamethasone, a synthetic corticosteroid, mitigates the glucocorticoid-receptor-mediated inflammation and accelerates tissue homeostasis towards disease resolution. To minimize non-target organ side effects arising from frequent and chronic use of dexamethasone, we designed biodegradable, lung-targeted microspheres with sustained release profiles. Dexamethasone-loaded lipopolymeric microspheres of PLGA (Poly Lactic-co-Glycolic Acid) and DPPC (Dipalmitoylphosphatidylcholine) stabilized with vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate) were prepared by a single emulsion technique that had a mean diameter of 8.83 ± 0.32 μm and were spherical in shape as revealed from electron microscopy imaging. Pharmacokinetic and biodistribution patterns studied in the lungs, liver, and spleen of Wistar rats showed high selectivity and targeting efficiency for the lung tissue (re 13.98). As a proof-of-concept, in vivo efficacy of the microspheres was tested in the lipopolysaccharide-induced ARDS model in rats. Inflammation markers such as IL-1β, IL-6, and TNF-α, quantified in the bronchoalveolar lavage fluid indicated major improvement in rats treated with dexamethasone microspheres by intravenous route. Additionally, the microspheres substantially inhibited the protein infiltration, neutrophil accumulation and lipid peroxidation in the lungs of ARDS bearing rats, suggesting a reduction in oxidative stress. Histopathology showed decreased damage to the pulmonary tissue upon treatment with the dexamethasone-loaded microspheres. The multipronged formulation technology approach can thus serve as a potential treatment modality for reducing lung inflammation in ARDS. An improved therapeutic profile would help to reduce the dose, dosing frequency and, eventually, the toxicity.

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“…Sriram et al demonstrated that hydrophobic drugs could be encapsulated in microspheres and administered intravenously to treat disease [5]. Sibghatullah et al used the method of spray drying to prepare gelatin microspheres encapsulating 5-fluorouracil with the particles size range of 5-15 µm for the treatment of lung cancer by intravenous injection, and the results showed that the drug-loaded microspheres improved the release time of the drug [6]. Thus, AKI therapy by intravenous injection of SAHA-loaded calcium alginate microspheres is a promising method.…”

Section: Introductionmentioning

confidence: 99%

Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment

Man

Wang

et al. 2022

Micromachines

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Acute kidney injury (AKI) is a common and severe problem associated with high morbidity, mortality, and healthcare costs. There are no reliable therapeutic interventions except dialysis that could improve survival, limit injury, or speed up recovery. Thus, it is essential to develop new therapies to treat AKI. Previous studies revealed that histone deacetylase inhibitor (HDACi) could attenuate renal injury and enhance kidney recovery in AKI. However, the hydrophobic nature of HDACi, such as vorinostat (SAHA), requires organic solvents to promote its dissolution, leading to inevitable detrimental effects. Herein, calcium alginate microspheres (CAM) were prepared by the microfluidic method as HDACi carriers to treat AKI by intravenous injection. First, we designed the structure of the microfluidic channel for the fabrication of the PDMS microfluidic chip in which the emulsion state of droplets was analyzed. As the flow rate increases, the continuous phase changed from laminar flow to the dripping pattern in the microfluidic device. Then, the CAM was fabricated by a W/O microfluidic emulsion template and the size of the microspheres was adjusted from 3 to 7 μm by the concentration of alginate and the flow rate of the continuous phase and dispersal phase. The higher degree of cross-linking of sodium alginate with calcium ions would lead to longer drug release time but lower swelling rates. Furthermore, we selected CAM with suitable sizes as the HDACi carrier and delivered the HDACi-loaded CAM to the AKI mice by intravenous tail injection. The in vivo results showed that the HDACi-loaded CAM could effectively reduce the renal regional inflammatory response and attenuate renal injury.

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Chemotherapeutic drug targeting to lungs by way of microspheres after intravenous administration

Cited by 14 publications

References 30 publications

Design of Pectin-Based Hydrogel Microspheres for Targeted Pulmonary Delivery

Design of Pectin-Based Hydrogel Microspheres for Targeted Pulmonary Delivery

Lung Targeted Lipopolymeric Microspheres of Dexamethasone for the Treatment of ARDS

Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment

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