TY - JOUR
T1 - Ambroxol hydrochloride loaded gastro-retentive nanosuspension gels potentiate anticancer activity in lung cancer (A549) cells
AU - Md, Shadab
AU - Abdullah, Samaa T.
AU - Alhakamy, Nabil A.
AU - Bani-Jaber, Ahmad
AU - Radhakrishnan, Ammu Kutty
AU - Karim, Shahid
AU - Shahzad, Naiyer
AU - Gabr, Gamal A.
AU - Alamoudi, Abdulmohsin J.
AU - Rizg, Waleed Y.
N1 - Funding Information:
Acknowledgments: The authors acknowledge with thanks DSR for technical and financial support.
Funding Information:
This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. (RG-12?166?42). The authors acknowledge with thanks DSR for technical and financial support.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosus-pensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK ) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis re-vealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.
AB - This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosus-pensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK ) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis re-vealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.
KW - Alginate
KW - Ambroxol
KW - Floating gels
KW - Kappa-carrageenan
KW - Lung cancer
KW - Nanosuspension
KW - Sustained release
UR - http://www.scopus.com/inward/record.url?scp=85121468551&partnerID=8YFLogxK
U2 - 10.3390/gels7040243
DO - 10.3390/gels7040243
M3 - Article
C2 - 34940303
AN - SCOPUS:85121468551
SN - 2310-2861
VL - 7
JO - Gels
JF - Gels
IS - 4
M1 - 243
ER -
