Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Abstract

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β 2 -adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.

In vitro bio-characterization of solid lipid nanoparticles of favipiravir in A549 human lung epithelial cancer cells

“…Additionally, determining the location, depth of penetration, and accumulation within the lung mucosal membranes by using the TBN-NVS particle dimensions is critical. 63 …”

Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate

“…The %EE is an important parameter in the design of novasomal formulations. The %EE of novasomes depends upon the stability of novasomes which depends upon the type of surfactant [ 30 ]. The values of %EE and drug loading are mentioned in Table S1 .…”

Effectiveness of the combination of terbutaline and budesonide inhalation in treating acute bronchial asthma during pregnancy

“…Some studies indicate that terbutaline, when administered via inhalation achieved the most effective and rapid results in asthma treatment. Onset was within 5 to 10 min, reached its peak effectiveness within an hour, and maintained its effects for approximately 4 h [13]. But there are also reports that daily application of β2 receptor agonists causes severe acute asthma attacks and sudden death.…”