TY - JOUR
T1 - Design of olmesartan medoxomil-loaded nanosponges for hypertension and lung cancer treatments
AU - Almutairy, Bjad K.
AU - Alshetaili, Abdullah
AU - Alali, Amer S.
AU - Ahmed, Mohammed Muqtader
AU - Anwer, Md Khalid
AU - Aboudzadeh, M. Ali
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/2
Y1 - 2021/7/2
N2 - Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = −18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m2 /g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly (p < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.
AB - Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = −18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m2 /g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly (p < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.
KW - Encapsulation
KW - Ethylcellulose
KW - Lung cancer
KW - Nanosponge
KW - Oral bioavailability
KW - Systolic blood pressure
UR - http://www.scopus.com/inward/record.url?scp=85110833862&partnerID=8YFLogxK
U2 - 10.3390/polym13142272
DO - 10.3390/polym13142272
M3 - Article
AN - SCOPUS:85110833862
SN - 2073-4360
VL - 13
JO - Polymers
JF - Polymers
IS - 14
M1 - 2272
ER -
