Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

Abstract

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions 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 revealed 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.

Development, Optimization, and In Vitro Evaluation of Novel Oral Long-Acting Resveratrol Nanocomposite In-Situ Gelling Film in the Treatment of Colorectal Cancer

“…On the other hand, the folds decrease for NA-Sp-Rv-1200 of BCL2 expression (Anti-apoptotic gene) were nearly 1.45, and 1.6 folds more than the Rv and blank, respectively. These gene expression results were suggesting enhanced apoptosis in NA-Sp-Rv-1200 on the molecular levels, and it came supportive for the previous evaluations [ 8 , 9 , 27 , 28 ].…”

“…The pellet was rinsed with PBS, fixed in 70% ethanol, and stored at −20 °C overnight. According to the manufacturer’s instructions, the cells were rinsed with PBS to extract the alcohol before being stained with PI and treated with RNAase and then analyzed using flow cytometry [ 27 , 28 ].…”

“…For reading, a Rotor gene RT-PCR device was used. Rotor-Gene 1.7.87 program was installed on the machine [ 27 , 28 ]. Table 4 displays the primer sequences used in the analysis.…”

Development and Evaluation of Ginkgo biloba/Sodium Alginate Nanocomplex Gel as a Long-Acting Formulation for Wound Healing

“…The binding, encapsulation, and amorphicity of the NG were reflected in the shear force applied by the alginate to form the nanogel found in the particle size analysis and TEM [ 29 , 31 ]. After all, the alginate nature and encapsulation were observed in the diffusion, rheology, and swelling studies [ 13 , 29 , 31 , 32 , 33 ].…”

“…The 5–10 mg optimized formulation sample was used for spectral analysis through Fourier transform infrared spectroscopy (FTIR) (Thermo-Scientific, NicoletiS10, Waltham, MA, USA). The ginkgo extract (GK), alginate (A), physical mixture (PM), and the optimum nanocomplex gel (NG) samples were scanned between 500 and 4000 cm −1 [ 9 , 30 , 31 , 33 ].…”