Liposomal encapsulation is a drug delivery strategy with many advantages, such as improved bioavailability, ability to carry large drug loads, as well as controllability and specificity towards various targeted diseased tissues. Currently, most preparation techniques require an additional extrusion or filtering step to obtain monodisperse liposomes with the size of less than 100 nm. In this study, a compact liposome extruder was designed at a cost of $4.00 and used to synthesize liposome suspensions with defined particle size and high homogeneity for Murrayafoline A (Mu-A) loading and release. The synthesized MuA-loaded liposomes displayed a biphasic drug release and remained stable under the storage condition of 4°C. They also significantly reduced the viability of HepG2 cells in the cancer spheroids by 25%. The low-cost, flexible liposome extruder would allow the researchers to study liposomes and their applications in a cost-effective manner.
Drug development is a complex and expensive process from new drug discovery to product approval. Most drug screening and testing rely on in vitro 2D cell culture models; however, they generally lack in vivo tissue microarchitecture and physiological functionality. Therefore, many researchers have used engineering methods, such as microfluidic devices, to culture 3D cells in dynamic conditions. In this study, a simple and low-cost microfluidic device was fabricated using Poly Methyl Methacrylate (PMMA), a widely available material, and the total cost of the completed device was USD 17.75. Dynamic and static cell culture examinations were applied to monitor the growth of 3D cells. α-MG-loaded GA liposomes were used as the drug to test cell viability in 3D cancer spheroids. Two cell culture conditions (i.e., static and dynamic) were also used in drug testing to simulate the effect of flow on drug cytotoxicity. Results from all assays showed that with the velocity of 0.005 mL/min, cell viability was significantly impaired to nearly 30% after 72 h in a dynamic culture. This device is expected to improve in vitro testing models, reduce and eliminate unsuitable compounds, and select more accurate combinations for in vivo testing.
Hepatocellular carcinoma is a common type of cancer associated with a high mortality rate. Among several bioactive compounds, Murrayafoline A (MuA) has been proved as a bio substance that exhibits great potentials in treating liver cancer. In order to overcome the high cytotoxicity and low solubility of MuA, a delivery system based on nanocarriers is necessary to deliver MuA towards the desired target. In the present study, 18β-glycyrrhetinic acid (GA), which is known as a ligand for liver targeting, was used to construct the cholesterol-poly (ethylene glycol)-glycyrrhetinic acid (GA-PEG-Chol) conjugate and liposome for MuA administration. The compound was then examined for therapeutic efficacy and safety in HUVEC and HepG2 cells in 2D and 3D cell cultures. Results have shown that MuA-loaded liposomes had IC50 value of 2 µM in HepG2 and had the cytosolic absorption of 8.83 ± 0.97 ng/105 cells, while The IC50 value of MuA-loaded liposomes in HUVEC cell lines was 15 µM and the the cytosolic absorption was recorded as 3.62 ± 0.61 cells. The drug test on the 3D cancer sphere platform of the HepG2 cancer sphere showed that MuA-loaded GA liposomes had the highest efficacy at a concentration of 100 µg/mL. In short, these results suggest that MuA-loaded GA liposomes have the potential for maintenance drug delivery and liver targeting.
Imidacloprid, acephate, and carbaryl are common insecticides that are extensively used in planting mango, a well-known fruit in Vietnam, to ease mango hopper issues. The accurate detection of pesticide residues is critical for mango export to meet quality criteria. This study developed a novel SERS platform by using polydimethylsiloxane (PDMS) to simulate the rose petal structure incorporated with a silver coating layer and silver nanoparticles (AgNPs) to detect imidacloprid, acephate, and carbaryl in mango fruits. In this paper, the rose petal PDMS/Ag-AgNPs replica was considered the most efficient substrate for SERS measurement with an EF of 4.7 × 107. The Raman spectra of the three insecticides obtained from the PDMS/Ag-AgNPs substrate were clearly observed with their characteristic peaks of 1105 cm−1 for imidacloprid, 1083 cm−1, and 1579 cm−1 for acephate, and 727 cm−1 and 1378 cm−1 for carbaryl. The application of PDMS/Ag-AgNPs substrate in quantitative analysis of the three pesticides in mango fruit was evaluated. As a result, the limit of detection was 0.02 mg/kg for imidacloprid, 5 × 10−5 mg/kg for acephate, and 5 × 10−3 mg/kg for carbaryl. The SERS result also revealed that the pesticide residues in the mango sample were within an acceptable limit. This suggested the possibility of the rose petal PDMS/Ag-AgNPs replica for rapid quantification of pesticide residues not only in mango fruit but also in many other agricultural products.
Murrayafoline A (MuA) is a natural compound with diverse biological activities, including cytotoxicity against cancer cells, but suffers from poor water solubility and low specificity. In order to improve the potential of MuA as a candidate for cancer treatment, MuA-loaded liposomes were prepared with the liposomal membrane consisting of dioleoylphosphatidylcholine and cholesterol. Dynamic light scattering measurements showed that the MuA-loaded liposomes had a z-average particle size of 104.3 ± 6.4 nm (mean ± SD; n = 3) and a polydispersity index of 0.15 ± 0.02 (mean ± SD; n = 3). The encapsulation efficiency was 55.3 ± 2.3% (mean ± SD; n = 3). The in vitro cytotoxicity of encapsulated MuA was attenuated at IC50 = 21.97 µg/mL compared to 6.24 µg/mL for free MuA, against HepG2. In contrast, MuA-loaded liposomes were significantly more effective at inhibiting cell growth in HepG2 cancer spheroids, which indicated that they were able to reach the interior layers of the microtumor. Taken together, these results showed that the encapsulation of MuA in liposomes is a good research direction to improve this natural compound’s potential as a candidate for cancer treatment.
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