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

被引:26
作者
Elkomy, Mohammed H. [1 ,2 ]
El Menshawe, Shahira F. [2 ]
Kharshoum, Rasha M. [2 ]
Abdeltwab, Amany M. [2 ]
Hussein, Raghda R. S. [3 ,4 ]
Hamad, Doaa S. [5 ]
Alsalahat, Izzeddin [6 ]
Aboud, Heba M. [2 ]
机构
[1] Jouf Univ, Coll Pharm, Dept Pharmaceut, Sakaka, Saudi Arabia
[2] Beni Suef Univ, Dept Pharmaceut & Ind Pharm, Fac Pharm, Bani Suwayf, Egypt
[3] Beni Suef Univ, Dept Clin Pharm, Fac Pharm, Bani Suwayf, Egypt
[4] Modern Univ Technol & Informat, Dept Clin Pharm, Fac Pharm, Cairo, Egypt
[5] Nahda Univ, Dept Pharmaceut, Fac Pharm, Bani Suwayf, Egypt
[6] Cardiff Univ, UK Dementia Res Inst Cardiff, Sch Med, Cardiff, Wales
关键词
Bronchial asthma; pulmonary targeting; terbutaline sulfate; novasomes; Box-Behnken design; pharmacokinetics; RESPONSE-SURFACE METHODOLOGY; BOX-BEHNKEN DESIGN; TRANSDERMAL DELIVERY; PHYSICOCHEMICAL CHARACTERIZATION; INHALATION TREATMENT; GROWTH-CONDITIONS; MEDIUM COMPONENTS; LUNG-CANCER; FORMULATION; LIPOSOMES;
D O I
10.1080/10717544.2022.2092236
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 beta(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, zeta 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.
引用
收藏
页码:2058 / 2071
页数:14
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