Tumor microenvironment responsive VEGF-antibody functionalized pH sensitive liposomes of docetaxel for augmented breast cancer therapy

Jain, Sanyog; Deore, Sandip Vikram; Ghadi, Rohan; Chaudhari, Dasharath; Kuche, Kaushik; Katiyar, Sameer S.

doi:10.1016/j.msec.2020.111832

Cited by 45 publications

(24 citation statements)

References 26 publications

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“…The entrapment efficiency decreased as the concentration of DOPE increased; this may be due to the structural flexibility of DOPE and the low transition temperature because the drug was not retained in the liposomes, leading to the decrease in the E.E of the liposomes. Similar effects were also reported by Jain, S. et al, 2021, [32], which also support the study with regard to the above-mentioned effect.…”

Section: Entrapment Efficiency (Ee)supporting

confidence: 92%

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pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

et al. 2022

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The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08–206.4 ± 2.26 nm, zeta potential was −17.8 ± 1.26 to −24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

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Section: Entrapment Efficiency (Ee)supporting

confidence: 92%

“…Moreover, there were no signs of lesions, disruption or deformation and any type of pathological changes within the vital organs of the test group in comparison with the control group. The lack of changes shows the safety and biocompatibility of the liposomal excipients [32,47,48].…”

Section: Acute Toxicity Studymentioning

confidence: 99%

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

et al. 2022

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“…Angiogenesis stimulating factors include a class of cytokines known as antigenic growth factors, which act to stimulate the formation of blood vessels ( 31 ). At present, angiogenic factors such as platelet-derived growth factor, fibroblast growth factor, transforming growth factor and VEGFA have been discovered ( 32 ), of which VEGFA plays a key role in tumor angiogenesis ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of microfibrillar‑associated protein 2 is closely associated with tumor angiogenesis and poor prognosis in hepatocellular carcinoma

2021

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Abnormal expression of microfibrillar-associated protein 2 (MFAP2), a key regulator of cellular differentiation, affects the occurrence and progression of tumors. However, the underlying role of MAFP2 in hepatocellular carcinoma (HCC) remains unclear. In the present study, patterns of MFAP2 expression in HCC were analyzed using sequencing data from The Cancer Genome Atlas database. Expression profiles of MFAP2, as well as those of epithelial-mesenchymal transition (EMT)-related proteins, were compared between HCC pathological sections and fresh tissues. Thereafter, associations between patterns of MFAP2 expression and the clinicopathological characteristics of patients, and identified risk factors associated with disease-free survival (DFS) and overall survival (OS), were determined. The functions of MFAP2 in the EMT-induced proliferation and migration of MHCC97H cells were investigated using in vitro experiments, and the effects of MFAP2 on vascular endothelial growth factor A (VEGFA)-induced tumor angiogenesis were also investigated. Upregulation of MFAP2 expression was observed in HCC, and was often accompanied by the abnormal expression of EMT-related marker proteins. In addition, analysis of clinical data from 94 patients with tumor tissues revealed a significant positive correlation between MFAP2 expression and low DFS and low OS following surgery. Through in vitro experimentation, silencing MFAP2 expression was shown inhibit EMT, which thereby inhibited cellular proliferation and migration. Moreover, downregulation of MFAP2 inhibited tumor angiogenesis via the inhibition of VEGFA. Taken together, these findings indicate that MFAP2 has the potential to predict the prognosis of patients with HCC. MFAP2 also induces tumor cell proliferation and migration through EMT, and promotes tumor blood vessel formation through VEGFA, suggesting that MFAP2 may be a potential therapeutic target for HCC.

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“…Soya lecithin (19 mg), cholesterol (19 mg), stearyl amine (2 mg), TPGS (5 mg) and NE (5 mg, 10% w/w) were lique ed in a 20 ml blend of chloroform (10% v/v) and kept under vacuum in a rotary evaporator (BUCHI, Flawil, Switzerland) for 30 minutes at 100 rpm to get rid of the solvent, and then proceeded in a vacuum oven for 4 hours to get rid of the organic solvent completely, and then hydration with HEPES buffer pH 7.4 was performed by repeated gentle heating at 100 rpm to get a concentration of 5 mg/mL. After that, the blend was sonicated in a cold-water bath for an optimum period to obtain smaller liposomes [32][33][34]. The developed preparation, were then characterized for encapsulation e ciency and in-vitro drug release pro le.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

“…The cells were incubated with coumarin-6 NE liposomes for 12 hours before being washed with HBSS (5X) to get rid of extracellular particles. The cells were examined using a confocal microscope (Olympus FV1000) at 400X magni cation for qualitative analysis [33].…”

Section: Cellular Uptake Studiesmentioning

confidence: 99%

Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

Kala

Chinni²

2022

Preprint

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PurposeNintedanib esylate (NE) is a kinase inhibitor designated for the cure of non-small cell lung cancer suffers from first-pass metabolism which resulted in low oral bioavailability (~4.7%). The intent of this exploration was to increase the oral bioavailability of NE by means of TPGS coated liposomes. MethodsThe NE-loaded TPGS coated liposomes were formulated by high-speed homogenization by optimizing process parameters like phospholipids: cholesterol molar ratio, drug loading and sonication time through the design of experiments. The drug's behaviour was studied using a variety of techniques, including physicochemical characterization, in-vitro and in-vivo studies. ResultsThe NE-liposomes had a particle size of 125±6.68 nm, entrapment efficiency of 88.64±4.12% and zeta potential of +46±2.75 mV. X-ray diffraction analysis revealed that NE had been converted to an amorphous state, while transmission electron microscope images showed spherical shape and smooth coating of TPGS on surface of liposomes. The formulation showed Higuchi kinetics with sustained drug release of 88.72 ± 3.40% in 24 hours. Cellular uptake of C-6 labelled liposomes was observed in A-549 cells and cytotoxicity testing revealed that NE-liposomes were more effective than marketed formulation Ofev®. Formulation remained in simulated fluids and for three months in stability chamber and. Liposomal oral bioavailability was ~6.23 times greater in sprague dawley male rats compared to marketed formulation Ofev®, according to in-vivo pharmacokinetic data. ConclusionNE-Liposomal formulations are better for oral administration compared to the marketed capsules because of the prolonged drug release and increased oral bioavailability as a result, the developed formulation can become a successful strategy in cancer chemotherapy.

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Tumor microenvironment responsive VEGF-antibody functionalized pH sensitive liposomes of docetaxel for augmented breast cancer therapy

Cited by 45 publications

References 26 publications

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

Upregulation of microfibrillar‑associated protein 2 is closely associated with tumor angiogenesis and poor prognosis in hepatocellular carcinoma

Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

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