scholarly journals Development of polymeric nanoparticles loaded with STAT3 inhibitory, Stattic, for targeted cancer therapy

2021 ◽  
Author(s):  
Hamed Masoumzadeh ◽  
Nasrin Hoseinzad ◽  
Sevda Jafari ◽  
Ali Shayanfar ◽  
Haleh Vaez ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Encapsulation Efficiency ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Fold Increase ◽  
Sh2 Domain ◽  
Burst Release ◽  
Scattering Method ◽  
Oncogenic Signaling ◽  
Constitutively Active

Background: STAT3 is an oncogenic signaling pathway found constitutively active in many types of human malignancies and plays a key role in cancer progression. Stattic is a small molecule, which selectively inhibits SH2 domain of STAT3. In most of the studies, stattic has been proposed as a promising strategy for inhibition of STAT3 in cancer cells harboring constitutively active STAT3. However, lack of proper formulation due to the poor water solubility and low bioavailability of stattic is a major limitation for its usage in clinic. The aim of this project was to develop poly(ethylene glycole)-block-poly(caprolactone) (PEG-b-PCL)-based polymeric micelles loaded with stattic and evaluate drug encapsulation efficiency and release in the developed formulations. Methods: In this experimental study, to prepare stattic loaded micellar formulations, co-solvent evaporation method was used. Mean diameter and polydispersity index (PDI) of micelles were defined by light scattering method. Encapsulated drug levels were measured using high performance liquid chromatography (HPLC). Data were analyzed using Graph pad prism software through one-way ANOVA analysis of variance. Results: Stattic was loaded in the polymeric micelles with encapsulation efficiency ranging from 40 to 73%. Drug loaded micelles were measured between 90 to 130 nm in size. PDI was obtained 0.3-1 and encapsulation of stattic in Polyethylene glycol-block-poly(α-benzyl carboxylate ε-caprolactone(PEG-b-PBCL) micellar formulation resulted in more than 6-fold increase in the water solubility of stattic (0.36 vs. 0.06 mg/mL). Respecting to high encapsulation efficiency, two micellar formulations were selected for further analysis that both of them released 70-80% of drug within the first hour, indicated burst release of drug. Conclusion: These findings show that PEG-b-PBCL copolymers can be a suitable vehicle for solubilization of stattic.

scholarly journals Inulin-Grafted Stearate (In-g-St) as the Effective Self-Assembling Polymeric Micelle: Synthesis and Evaluation for the Delivery of Betamethasone

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Gholamabbas Chehardoli ◽  
Parham Norouzian ◽  
Farzin Firozian
Keyword(s):  
Zeta Potential ◽  
Sustained Release ◽  
Targeted Delivery ◽  
Encapsulation Efficiency ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Polymeric Micelle ◽  
Water Soluble ◽  
Burst Release ◽  
Potential Measurement

Background. Betamethasone as a corticosteroid drug is commonly used for the treatment of rheumatoid arthritis. Unfortunately, betamethasone is a low water-soluble drug and its efficacy is low. So an attractive strategy is the targeted delivery of betamethasone to the damaged joint using polymeric micelle-based carriers. Methods. Inulin-grafted stearate (In-g-St) was synthesized via the reaction of stearoyl chloride and inulin, then characterized by FT-IR and H-NMR. In-g-St forms micelles in the presence of betamethasone. The prepared polymeric micelles were characterized for size, zeta potential, drug loading, particles’ morphology, critical micelle concentration (CMC), and encapsulation efficiency. So sustained release polymeric micelles of betamethasone were developed by employing In-g-St. Results. The measurement of particle size showed a mean diameter of 60 and 130 nm for 10% and 20% drug-loaded micelles, respectively, and SEM showed that the particle’s morphologies are spherical. Zeta potential measurement for the drug-containing micelles showed a value of -11.8 mV. Drug loading efficiency and the encapsulation efficiency were 6.36% and 63.6%, as well as 18.97% and 94.88% for 10% and 20%, respectively. 20% drug-loaded polymer showed a small burst release of betamethasone at the first 3 h which was followed by sustained release in the next 24 h. Furthermore, the formula with 10% exhibited good sustained release properties except for the minor initial burst release. Conclusion. Data from the zeta potential, CMC, drug loading capacity, and in vitro drug release studies indicated that In-g-St polymeric micelles can be suitable candidates for the efficient delivery of hydrophobic drugs like betamethasone.

scholarly journals The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Maria Natalia Calienni ◽  
Daniela Maza Vega ◽  
C. Facundo Temprana ◽  
María Cecilia Izquierdo ◽  
David E. Ybarra ◽  
...  
Keyword(s):  
Side Effects ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Skin Penetration ◽  
Distribution Volume ◽  
And Performance ◽  
Oral Doses ◽  
Advanced Basal Cell Carcinoma

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

Biodegradable polymers-based nanoparticles to enhance the antifungal efficacy of fluconazole against Candida albicans

2021 ◽  
Vol 22 ◽  
Author(s):  
Noha Saleh ◽  
Soha Elshaer ◽  
Germeen Girgis
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Encapsulation Efficiency ◽  
Water Solubility ◽  
In Vitro Release ◽  
Double Emulsion ◽  
Dilution Method ◽  
Ft Ir ◽  
Antifungal Efficacy

Background: Fluconazole (FLZ), a potent antifungal medication, is characterized by poor water solubility that reduced its antifungal efficacy. Objective: This study aimed to prepare FLZ-loaded polymeric nanoparticles (NPs) by using different polymers and techniques as a mean of enhancing the antifungal activity of FLZ. Methods: NP1, NP2, and NP3 were prepared by the double emulsion/solvent evaporation method using PLGA, PCL, and PLA, respectively. The ionotropic pre-gelation technique was applied to prepare an alginate/chitosan-based formulation (NP4). Particle size, zeta potential, encapsulation efficiency, and loading capacity were characterized. FT-IR spectra of FLZ, the polymers, and the prepared NPs were estimated. NP4 was selected for further in-vitro release evaluation. The broth dilution method was used to assess the antifungal activity of NP4 using a resistant clinical isolate of Candida albicans. Results: The double emulsion method produced smaller-sized particles (<390 nm) but with much lower encapsulation efficiency (< 12%). Alternatively, the ionic gelation method resulted in nanosized particles with a markedly higher encapsulation efficiency of about 40%. The FT-IR spectroscopy confirmed the loading of the FLZ molecules in the polymeric network of the prepared NPs. The release profile of NP4 showed a burst initial release followed by a controlled pattern up to 24 hours with a higher percent released relative to the free FLZ suspension. NP4 was able to reduce the value of MIC of FLZ by 20 times. Conclusion: The antifungal activity of FLZ against C. albicans was enhanced markedly via its loading in the alginate/chitosan-based polymeric matrix of NP4.

scholarly journals Reactive Oxygen Species: A Key Constituent in Cancer Survival

2018 ◽  
Vol 13 ◽  
pp. 117727191875539 ◽  
Author(s):  
Seema Kumari ◽  
Anil Kumar Badana ◽  
Murali Mohan G ◽  
Shailender G ◽  
RamaRao Malla
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Progression ◽  
Cancer Survival ◽  
Reactive Oxygen ◽  
Redox Balance ◽  
High Morbidity ◽  
Oxygen Species ◽  
Oncogenic Signaling ◽  
Cancer Cell Death ◽  
New Strategy

Background: Cancer is one of the major heterogeneous disease with high morbidity and mortality with poor prognosis. Elevated levels of reactive oxygen species (ROS), alteration in redox balance, and deregulated redox signaling are common hallmarks of cancer progression and resistance to treatment. Mitochondria contribute mainly in the generation of ROS during oxidative phosphorylation. Elevated levels of ROS have been detected in cancers cells due to high metabolic activity, cellular signaling, peroxisomal activity, mitochondrial dysfunction, activation of oncogene, and increased enzymatic activity of oxidases, cyclooxygenases, lipoxygenases, and thymidine phosphorylases. Cells maintain intracellular homeostasis by developing an immense antioxidant system including catalase, superoxide dismutase, and glutathione peroxidase. Besides these enzymes exist an important antioxidant glutathione and transcription factor Nrf2 which contribute in balancing oxidative stress. Reactive oxygen species–mediated signaling pathways activate pro-oncogenic signaling which eases in cancer progression, angiogenesis, and survival. Concomitantly, to maintain ROS homeostasis and evade cancer cell death, an increased level of antioxidant capacity is associated with cancer cells. Conclusions: This review focuses the role of ROS in cancer survival pathways and importance of targeting the ROS signal involved in cancer development, which is a new strategy in cancer treatment.

scholarly journals Nanopolyphenols: a review of their encapsulation and anti-diabetic effects

2020 ◽  
Vol 2 (8) ◽  
Author(s):  
Theresa F. Rambaran
Keyword(s):  
Functional Food ◽  
Encapsulation Efficiency ◽  
Water Solubility ◽  
Drug Loading ◽  
Therapeutic Agents ◽  
Low Ph ◽  
Free Form ◽  
Pharmaceutical Development ◽  
Curcumin Nanoparticles ◽  
Treatment Of Diabetes

AbstractPolyphenols are believed to possess numerous health benefits and can be grouped as phenolic acids, flavonoids or non-flavonoids. Research involving the synthesis of nanopolyphenols has attracted interest in the areas of functional food, nutraceutical and pharmaceutical development. This is in an effort to overcome current challenges which limit the application of polyphenols such as their rapid elimination, low water-solubility, instability at low pH, and their particle size. In the synthesis of nanopolyphenols, the type of nanocarrier used, the nanoencapsulation technique employed and the type of polymers that constitute the drug delivery system are crucial. For this review, all mentioned factors which can influence the therapeutic efficacy of nanopolyphenols were assessed. Their efficacy as anti-diabetic agents was also evaluated in 33 publications. Among these were phenolic acid (1), flavonoids (13), non-flavonoids (17) and polyphenol-rich extracts (2). The most researched polyphenols were quercetin and curcumin. Nanoparticles were the main nanocarrier and the size of the nanopolyphenols ranged from 15 to 333 nm with encapsulation efficiency and drug loading capacities of 56–97.7% and 4.2–53.2%, respectively. The quantity of nanomaterial administered orally ranged from 1 to 300 mg/kg/day with study durations of 1–70 days. Most studies compared the effect of the nanopolyphenol to its free-form and, in all but three cases, significantly greater effects of the former were reported. Assessment of the polyphenol to understand its properties and the subsequent synthesis of its nanoencapsulated form using suitable nanocarriers, polymers and encapsulation techniques can result in effective therapeutic agents for the treatment of diabetes.

scholarly journals Alteration in transforming growth factor-β receptor expression in gallbladder disease: implications of chronic cholelithiasis and chronic Salmonella typhi infection

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Yogesh D. Walawalkar ◽  
Yatindra Vaidya ◽  
Vijayashree Nayak
Keyword(s):  
Growth Factor ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Receptor Gene ◽  
Gallbladder Disease ◽  
Fold Increase ◽  
Transforming Growth Factor Β ◽  
Salmonella Typhi ◽  
Receptor Expression ◽  
Β Receptor

Gallbladder cancer prevalence is ever increasing with <em>Salmonella typhi</em> chronic infection being one of the predisposing factors. Altered ratios or expression of transforming growth factor-β (TGF-β) receptors and changes in its function are associated with loss in anti-proliferative effects of TGF-β and cancer progression. Using reverse transcriptase polymerase chain reaction we monitor any changes in TGF-β receptor gene expression. We simultaneously screen for <em>S. typhi</em> within the samples. From 73 patients undergoing cholecystectomy 39-50% had significant expression (P&lt;0.05) of TGF-β receptor (TβR)- I and TβR-II during chronic cholelithiasis as compared to the remaining 19-23% with acute chronic cholelithiasis. There was no significant increase in TβR-III receptor expression. Patient’s positive for <em>S. typhi</em> (7/73) did not show any significant changes in expression of these receptors, thus indicating no direct relation in regulating the host TGFβ-signaling pathway. Further analysis on expression of downstream Smad components revealed that patients with up-regulated TGFβ receptor expression show &gt;2-fold increase in the RSmads and Co-Smads with a &gt;2-fold decrease in I-Smads. Thus gain of TβR-I and II expression in epithelial cells of the gallbladder was associated with chronic inflammatory stages of the gallbladder disease.

scholarly journals The Cigarette Smoke Carcinogen Benzo[a]pyrene Enhances Human Papillomavirus Synthesis

2007 ◽  
Vol 82 (2) ◽  
pp. 1053-1058 ◽  
Author(s):  
Samina Alam ◽  
Michael J. Conway ◽  
Horng-Shen Chen ◽  
Craig Meyers
Keyword(s):  
Human Papillomavirus ◽  
Cigarette Smoke ◽  
Cancer Progression ◽  
Fold Increase ◽  
Epidemiological Studies ◽  
Low Concentrations ◽  
Virion Morphogenesis ◽  
High Concentrations ◽  
Cervical Cells ◽  
Viral Titers

ABSTRACT Epidemiological studies suggest that cigarette smoke carcinogens are cofactors which synergize with human papillomavirus (HPV) to increase the risk of cervical cancer progression. Benzo[a]pyrene (BaP), a major carcinogen in cigarette smoke, is detected in the cervical mucus and may interact with HPV. Exposure of cervical cells to high concentrations of BaP resulted in a 10-fold increase in HPV type 31 (HPV31) viral titers, whereas treatment with low concentrations of BaP resulted in an increased number of HPV genome copies but not an increase in virion morphogenesis. BaP exposure also increased HPV16 and HPV18 viral titers. Overall, BaP modulation of the HPV life cycle could potentially enhance viral persistence, host tissue carcinogenesis, and permissiveness for cancer progression.

Emulsion electrospun polylactic acid/Apocynum venetum nanocellulose nanofiber membranes with controlled sea buckthorn extract release as a drug delivery system

2020 ◽  
pp. 004051752097017
Author(s):  
Lu Wang ◽  
Chenmeizi Wang ◽  
Ling Wang ◽  
Qingle Zhang ◽  
Ying Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Polylactic Acid ◽  
Encapsulation Efficiency ◽  
Sea Buckthorn ◽  
Burst Release ◽  
Nanofiber Membrane ◽  
Apocynum Venetum ◽  
Nanofiber Membranes ◽  
Sheath Structure

Prolonging the duration of drug action and reducing toxicity play a vital role in wound administration as they reduce the chance of infection and decrease complications and cost. This study reports the natural antioxidant procyanidins extracted from sea buckthorn (SBT) and laboratory-manufactured Apocynum venetum cellulose nanofiber as core drugs. The sustained-release nanofiber membrane was prepared by electrospinning on polylactic acid/polyvinyl pyrrolidone nanofibers. High-performance liquid chromatography-mass spectrometry was used to identify the phenolic compounds in SBT extracts and confirmed the presence of procyanidins with a content of 0.0345 mg/g. The nanofiber membrane was characterized through transmission electron microscopy, encapsulation efficiency, in vitro drug-release study and antioxidant assay. The results indicated that the extracted procyanidins were successfully encapsulated in the core–sheath structure nanofibers, and the encapsulation efficiency of nanofiber membranes reached 83.84%. In vitro measurements of the delivery showed this core–sheath structure could significantly alleviate the drug burst release, which is followed by a linear and smooth release within 30 hours. Further tests showed that the removal efficiency of 2,2-diphenyl-1-picrylhydrazyl reached 88.62%, indicating that the membranes had high antioxidant activity. This work implies that the combination of Apocynum venetum nanocellulose and emulsion electrospun fibers has promising potential applications in tissue engineering or drug delivery.

Development and Characterization of Olanzapine Loaded Poly(lactide-co-glycolide) Microspheres for Depot Injection: In vitro and In vivo Release Profiles

2019 ◽  
Vol 16 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Fahad Pervaiz ◽  
Mahmood Ahmad ◽  
Lihong Li ◽  
Ghulam Murtaza
Keyword(s):  
Bulk Density ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
Infrared Spectrometry ◽  
Burst Release ◽  
In Vivo Release ◽  
Depot Injection ◽  
Vitro Release

Purpose: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance. Methods: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats. Results: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 μm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density. Conclusion: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.

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