scholarly journals Development of a Thymoquinone Polymeric Anticancer Nanomedicine through Optimization of Polymer Molecular Weight and Nanoparticle Architecture

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 811
Author(s):  
Suhair Sunoqrot ◽  
Malek Alfaraj ◽  
Ala’a M. Hammad ◽  
Violet Kasabri ◽  
Dana Shalabi ◽  
...  
Keyword(s):  
Drug Release ◽  
Human Cancer ◽  
Nigella Sativa ◽  
Drug Loading ◽  
Fold Increase ◽  
Hydrodynamic Diameter ◽  
Maximum Plasma ◽  
Human Cancer Cell Lines ◽  
Loading Efficiency

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (Cmax) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations.

Biodegradable Amphiphilic Tri-Block Copolymeric Nanoparticles for Controlled MTB Drug Delivery

2012 ◽  
Vol 584 ◽  
pp. 460-464 ◽  
Author(s):  
M Gajendiran ◽  
S. Balasubramanian
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Powder Xrd ◽  
Burst Release ◽  
In Vitro Drug Release ◽  
Drug Content ◽  
Loading Efficiency ◽  
Release Studies ◽  
Drug Loading Efficiency

. A series of biodegradable amphiphilic tri-block copolymers (PLGA–PEG–PLGA) have been derived from the diblock copolymer poly (lactic–co–glycolic acid (PLGA)) and polyethylene glycol (PEG). The mycobacterium tuberculosis (MTB) drug pyrazinamide (PZA) loaded polymer nanoparticles (NPs) have been prepared by probe-sonication followed by w/o/w double emulsification technique. The copolymers have been characterized by FTIR and 1HNMR spectroscopic techniques, TG-DTA analysis, GPC analysis and powder XRD pattern. The MTB drug loaded polymeric NPs have been characterized by FESEM, powder XRD, HRTEM and XPS analysis. The drug loading efficiency, drug content and in vitro drug release studies have been carried out by spectrophotometry. The drug loading efficiency and drug content of triblock copolymeric NPs were higher than these of diblock copolymeric microparticles (MPs). The in vitro drug release studies indicate that the NPs exhibit initial burst release followed by controlled release of PZA for longer durations. The drug release kinetics mechanism has been evaluated by zero order, first order, Korsemeyer-Peppas (KP) and Higuchi models.

scholarly journals Molecular Dynamics Simulation, Characterization and In Vitro Drug Release of Isoniazid Loaded Poly-ε-caprolactone Magnetite Nanocomposite

2020 ◽  
Vol 26 (4) ◽  
pp. 406-413
Author(s):  
Aram dokht khatibi Khatibi ◽  
Zarrin Eshaghi ◽  
Hamid Mosaddeghi ◽  
Davoud Balarak
Keyword(s):  
Molecular Dynamics ◽  
Drug Release ◽  
Drug Loading ◽  
Dynamics Simulation ◽  
Radius Of Gyration ◽  
Drug Content ◽  
Loading Efficiency ◽  
Drug Loading Efficiency ◽  
Potential Tool

Background: This study reports on the development of a controlled-release isoniazid (INH) drug delivery system using poly-є-caprolactone (PCL) functionalized magnetite-nanoparticles (MNPs), as a theoretical potential tool for tuberculosis (TB) chemotherapy. Method: The magnetite Fe3O4 core was fabricated by the co-precipitation method and coated with PCL by emulsion polymerization. INH was loaded onto the PCL-MNP surface to shape an INH-PCL-MNP nanocomposite. Deposing the INH on the nanocomposite surface was demonstrated through the molecular dynamics simulations. To investigate the stability of the polymer, the root-mean-square deviation (RMSD) and the radius of gyration (Rg) were calculated. The composite was characterized by Scanning electron microscopy (SEM) and X-Ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Mycobacterium tuberculosis was used to assess the antimicrobial activity of the nanoparticles. The drug loading efficiency, drug content, and in-vitro release behavior of the INH-PCL-MNPs were evaluated by UV–Vis spectrophotometry. Results: RMSD of PCL show that the structure of polymer after 40 ns is stable. INH molecules interested to spend more time close to the polymer. Rg of PCL indicated that PCL folded and radius of gyration changed near 1nm. The drug loading efficiency and drug content of the NPs were 720±46 mg/g and 69.3±3.8 (%), respectively. The compound showed a strong level of activity in-vitro. The amount of drug release at all times was above the minimum inhibitory concentration (MIC) (6 μg/ml). Conclusion: INH-PCL-MNP nanocomposite have been effectively used as a potential tool to treat TB infections and a magnetic drug carrier system.

scholarly journals Effect of a Drug Delivery System Made of Quercetin Formulated into PEGylation Liposomes on Cervical Carcinoma In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jian Li ◽  
Zhen Li ◽  
Yanting Gao ◽  
Shihe Liu ◽  
Kun Li ◽  
...  
Keyword(s):  
Cervical Carcinoma ◽  
Slow Release ◽  
Malignant Tumors ◽  
Human Cancer ◽  
Drug Loading ◽  
Human Cancer Cell Lines ◽  
Solubility Improvement ◽  
Wide Range

Quercetin is a well-known flavonoid for its potent antitumor and antiproliferative effects on a wide range of human cancer cell lines. However, the delivery of quercetin is challenging due to its extreme insolubility in water. The intention of this study was to evaluate the antitumor effect of quercetin-loaded PEGylated liposomes (PEG-Que-NLs) in vitro and in vivo. We first prepared PEG-Que-NLs by method of thin film hydration; further determined, the optimum ratios of quercetin to Soybean phosphatidylcholine (SPC), to cholesterol (CHL), and to PEG-4000 were 1 : 8, 1 : 2, and 1 : 2 ( w / w ), respectively, and the optimal hydration temperature was 55°C when the mean vesicle diameter and apparent Zeta potential of PEG-Que-NLs were found to be 171.3 ± 10.4  nm and − 13.1 ± 2.1  mV, respectively; the encapsulation efficiency and the drug loading of PEG-Que-NLs were 81.25 ± 3.12 % and 8.5 ± 0.77 % , respectively. Drug release study in vitro showed that PEG-Que-NLs exhibited a slow-release effect without significant burst effect. Furthermore, the inhibition effect of PEG-Que-NLs on HeLa cells was considerably higher than free quercetin (free-Que) and quercetin liposomes (Que-NLs). Intravenous injection of PEG-Que-NLs into U14 bearing mouse models inhibited the cervical carcinoma growth significantly, and the tumor inhibition rate was much higher than free-Que and Que-NLs. These results of this study indicated that PEG-Que-NLs exhibited potential application prospects in the treatment of malignant tumors because of its tumor targeting, slow-release properties, and the solubility improvement of quercetin.

Solid Lipid Nanoparticles for Topical Delivery of Acitretin for the Treatment of Psoriasis by Design of Experiment

2020 ◽  
Vol 12 (2) ◽  
pp. 4474-4491
Author(s):  
Rajkumar Aland ◽  
Ganesan M ◽  
P. Rajeswara Rao ◽  
Bhikshapathi D. V. R. N.
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Solid Lipid Nanoparticles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
Tem Analysis ◽  
In Vitro Drug Release ◽  
Solid Lipid

The main objective for this investigation is to develop and optimize the solid lipid nanoparticles formulation of acitretin for the effective drug delivery. Acitretin loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s orthogonal array with eight parameters that could affect the particle size and entrapment efficiency. Based on the results from the analyses of the responses obtained from Taguchi design, three different independent variables including surfactant concentration (%), lipid to drug ratio (w/w) and sonication time (s) were selected for further investigation using central composite design. The  lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. TEM analysis has demonstrated the presence of individual nanoparticles in spherical shape and the results were compatible with particle size measurements.  In vitro drug release of optimized SLN formulation (F2) was found to be 95.63 ± 1.52%, whereas pure drug release was 30.12 after 60 min and the major mechanism of drug release follows first order kinetics release data for optimized formulation (F2) with non-Fickian (anomalous) with a strong correlation coefficient (R2 = 0.94572) of Korsemeyer-Peppas model. The total drug content of acitretin gel formulation was found to 99.86 ± 0.012% and the diameter of gel formulation was 6.9 ± 0.021 cm and that of marketed gel was found to be 5.7 ± 0.06 cm, indicating better spreadability of SLN based gel formulation. The viscosity of gel formulation at 5 rpm was found to be 6.1 x 103 ± 0.4 x 103 cp. The release rate (flux) of acitretin across the membrane and excised skin differs significantly, which indicates about the barrier properties of skin. The flux value for SLN based gel formulation (182.754 ± 3.126 μg cm−2 h−1) was found to be higher than that for marketed gel (122.345 ± 4.786 μg cm−2 h−1). The higher flux and Kp values of SLN based gel suggest that it might be able to enter the skin easily as compared with marketed gel with an advantage of low interfacial tension of the emulsifier film that ensures an excellent contact to the skin. This topically oriented SLN based gel formulation could be useful in providing site-specific dermal treatment of psoriasis

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

scholarly journals Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3923
Author(s):  
Adel A.-H. Abdel-Rahman ◽  
Amira K. F. Shaban ◽  
Ibrahim F. Nassar ◽  
Dina S. EL-Kady ◽  
Nasser S. M. Ismail ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

Preparation, evaluation, and in vitro release of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules

2020 ◽  
pp. 1-9
Author(s):  
Yunhong Wang ◽  
Rong Hu ◽  
Yanlei Guo ◽  
Weihan Qin ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Release Rate ◽  
Orthogonal Design ◽  
Drug Loading ◽  
In Vitro Release ◽  
Core Material ◽  
Evaluation Indexes ◽  
Vitro Release

OBJECTIVE: In this study we explore the method to prepare tanshinone self-microemulsifying sustained-release microcapsules using tanshinone self-microemulsion as the core material, and chitosan and alginate as capsule materials. METHODS: The optimal preparation technology of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules was determined by using the orthogonal design experiment and single-factor analysis. The drug loading and entrapment rate were used as evaluation indexes to assess the quality of the drug, and the in vitro release rate was used to evaluate the drug release performance. RESULTS: The best technology of chitosan-alginate tanshinone self-microemulsifying sustained-release microcapsules is as follows: the concentration of alginate is 1.5%, the ratio of tanshinone self-microemulsion volume to alginate volume to chitosan mass is 1:1:0.5 (ml: ml: g), and the best concentration of calcium chloride is 2.0%. To prepare the microcapsules using this technology, the drug loading will be 0.046%, the entrapment rate will be 80.23%, and the 24-hour in vitro cumulative release rate will be 97.4%. CONCLUSION: The release of the microcapsules conforms to the Higuchi equation and the first-order drug release model and has a good sustained-release performance.

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