scholarly journals Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1905 ◽  
Author(s):  
Jose ◽  
A. ◽  
Sebastian ◽  
H. ◽  
A. ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Plga Nanoparticles ◽  
Cell Uptake ◽  
Scanning Calorimetry ◽  
Cytotoxicity Studies ◽  
Anti Cancer ◽  
Mcf 7

Targeted drug delivery systems are commonly used to improve the therapeutic index of anti-cancer drugs by increasing their selectivity and reducing systemic distribution and toxicity. Ligand-conjugated nanoparticles (NPs) can be effectively applied for active chemotherapeutic targeting to overexpressed receptors of tumor cells. In this study, transferrin (Tf) was successfully conjugated with poly-l-lactic-co-glycolic acid (PLGA) using ethylene diamine confirmed by NMR, for the loading of docetaxel trihydrate (DCT) into PLGA nanoparticles (NPs). The DCT-loaded Tf-conjugated PLGA NPs were produced by an emulsion-solvent evaporation technique, and a 32 full factorial design was used to optimize the nanoparticle formulations. The DCT-loaded Tf-conjugated PLGA NPs were characterized by FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction (PXRD), TEM, particle size, and zeta potential analysis. In vitro release kinetics confirmed that release of DCT from the designed formulations followed a zero-order kinetics and a diffusion controlled non-Fickian release profile. The DCT-loaded Tf-conjugated PLGA NPs were evaluated in vitro in MCF-7 cells for bioactivity assessment. Cytotoxicity studies confirmed that the Tf-conjugated PLGA NPs were more active than the non-conjugated counterparts. Cell uptake studies re-confirmed the ligand-mediated active targeting of the formulated NPs. From the cell cycle analysis, the anti-cancer activity of DCT-loaded Tf-conjugated PLGA NPs was shown to occur by arresting the G2/M phase.

Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

2020 ◽  
Vol 16 (3) ◽  
pp. 340-349
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Ernest Hamel ◽  
Zahra Shahsavari ◽  
Mohsen Alipour ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Neuropathy ◽  
Cell Line ◽  
Normal Cell ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Cell Line ◽  
Anti Cancer ◽  
Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

scholarly journals Formulation and development of metformin-loaded microspheres using Khaya senegalensis (Meliaceae) gum as co-polymer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Chukwuebuka H. Ozoude ◽  
Chukwuemeka P. Azubuike ◽  
Modupe O. Ologunagba ◽  
Sejoro S. Tonuewa ◽  
Cecilia I. Igwilo
Keyword(s):  
Controlled Release ◽  
Sodium Alginate ◽  
Release Kinetics ◽  
Drug Carrier ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Metformin Hydrochloride ◽  
Scanning Calorimetry ◽  
Khaya Senegalensis

Abstract Background Khaya gum is a bark exudate from Khaya senegalensis (Maliaecae) that has drug carrier potential. This study aimed to formulate and comparatively evaluate metformin-loaded microspheres using blends of khaya gum and sodium alginate. Khaya gum was extracted and subjected to preformulation studies using established protocols while three formulations (FA; FB and FC) of metformin (1% w/v)-loaded microspheres were prepared by the ionic gelation method using 5% zinc chloride solution as the cross-linker. The formulations contained 2% w/v blends of khaya gum and sodium alginate in the ratios of 2:3, 9:11, and 1:1, respectively. The microspheres were evaluated by scanning electron microscopy, Fourier transform-infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, swelling index, and in vitro release studies. Results Yield of 28.48%, pH of 4.00 ± 0.05, moisture content (14.59% ± 0.50), and fair flow properties (Carr’s index 23.68 ± 1.91 and Hausner’s ratio 1.31 ± 0.03) of the khaya gum were obtained. FTIR analyses showed no significant interaction between pure metformin hydrochloride with excipients. Discrete spherical microspheres with sizes ranging from 1200 to 1420 μm were obtained. Drug entrapment efficiency of the microspheres ranged from 65.6 to 81.5%. The release of the drug from microspheres was sustained for the 9 h of the study as the cumulative release was 62% (FA), 73% (FB), and 80% (FC). The release kinetics followed Korsmeyer-Peppas model with super case-II transport mechanism. Conclusion Blends of Khaya senegalensis gum and sodium alginate are promising polymer combination for the preparation of controlled-release formulations. The blend of the khaya gum and sodium alginate produced microspheres with controlled release properties. However, the formulation containing 2:3 ratio of khaya gum and sodium alginate respectively produced microspheres with comparable controlled release profiles to the commercial brand metformin tablet.

scholarly journals An Innovative Formulation Based on Nanostructured Lipid Carriers for Imatinib Delivery: Pre-Formulation, Cellular Uptake and Cytotoxicity Studies

Nanomaterials ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 250
Author(s):  
Evren Gundogdu ◽  
Emine-Selin Demir ◽  
Meliha Ekinci ◽  
Emre Ozgenc ◽  
Derya Ilem-Ozdemir ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Cellular Uptake ◽  
Enzyme Inhibitor ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Nanostructured Lipid Carrier ◽  
Loading Capacity ◽  
Cytotoxicity Studies

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification–sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and −32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer–Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

scholarly journals Lutein-Loaded, Biotin-Decorated Polymeric Nanoparticles Enhance Lutein Uptake in Retinal Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 798 ◽  
Author(s):  
Pradeep Kumar Bolla ◽  
Vrinda Gote ◽  
Mahima Singh ◽  
Manan Patel ◽  
Bradley A. Clark ◽  
...  
Keyword(s):  
Polymeric Nanoparticles ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
In Vitro Release ◽  
Age Related Macular Degeneration ◽  
Scanning Calorimetry ◽  
Retinal Cells ◽  
Age Related ◽  
Cytotoxicity Studies

Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood–retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA–PEG–biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA–PEG–biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA–PEG–biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA–PEG–biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA–PEG–biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.

scholarly journals DESIGN, OPTIMIZATION AND IN VITRO EVALUATION OF ANTIFUNGAL ACTIVITY OF NANOSTRUCTURED LIPID CARRIERS OF TOLNAFTATE

2019 ◽  
pp. 109-115
Author(s):  
AHMED GARDOUH ◽  
Samar H. Faheim ◽  
Samar M. Solyman
Keyword(s):  
Zeta Potential ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Homogenization Method ◽  
Nanostructured Lipid Carriers ◽  
Scanning Calorimetry ◽  
Release Study ◽  
Vitro Release

Objective: The main purpose of this work was to prepare tolnaftate (TOL) loaded nanostructured lipid carriers (NLCs), Evaluate its characteristics and in vitro release study. Methods: Tolnaftate loaded Nanostructured lipid carriers were prepared by the high shear homogenization method using different liquid lipids types (DERMAROL DCO® and DERMAROL CCT®) and concentrations, different concentration ratios of tween80® to span20® and different homogenization speeds. All the formulated nanoparticles were subjected to particle size (PS), zeta potential (ZP), polydispersity index (PI), drug entrapment efficiency (EE), Differential Scanning Calorimetry (DSC), Transmission Electron microscopy (TEM), release kinetics and in vitro release study was determined. Results: The results revealed that NLC dispersions had spherical shapes with an average size between 154.966±1.85 nm and 1078.4±103.02 nm. High entrapment efficiency was obtained with negatively charged zeta potential with PDI value ranging from 0.291±0.02 to 0.985±0.02. The release profiles of all formulations were characterized by a sustained release behavior over 24 h and the release rates increased as the amount of surfactant decreased. The release rate of TOL is expressed following the theoretical model by Higuchi. Conclusion: From this study, It can be concluded that NLCs are a good carrier for tolnaftate delivery

scholarly journals Preparation, Characterization and Dissolution Behaviour of Freeze Dried Complexes of Curcumin-Gamma Cyclodextrin

2021 ◽  
pp. 17-26
Author(s):  
M. J. Ansari ◽  
K. Kohli ◽  
J. Ali
Keyword(s):  
Inclusion Complexes ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Stoichiometric Ratio ◽  
Scanning Calorimetry ◽  
First Order ◽  
Rate Of Dissolution ◽  
Freeze Dried ◽  
Gamma Cyclodextrin

The aim of the current research was to develop and characterize curcumin-gamma cyclodextrin inclusion complexes in order to enhance solubility and rate of dissolution of poorly soluble curcumin. Based on the stoichiometric ratio of 1:1, the inclusion complexes of curcumin with γ-cyclodextrin were prepared by freeze drying method. The prepared dried and solidified inclusion complexes were characterized with the help of infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. The comparative evaluation of solubility and rate of dissolution were investigated and compared with pure curcumin. Dissolution study demonstrated only 10% release from pure curcumin at 1 hour as opposed of approximately 72% release form freeze dried curcumin complexes. The freeze dried complexes exhibited almost complete release after 5 hours while only 34% release was observed from the pure curcumin during the same time period. Therefore, the freeze dried complex provided approximately 3 to 7-fold enhancement in the dissolution and release of curcumin over a period of 6 hours of dissolution testing.  The kinetics of the in vitro release behaviors of the curcumin and curcumin complexes were investigated by applying various models such as zero order, first order, Higuchi and Peppas models. The release of the curcumin was observed to follow the first order release kinetics, since the correlation coefficient (R2) for the first order was the highest in comparison to other kinetic models.

scholarly journals Characterization of Ketoprofen/Methyl-β-Cyclodextrin Complexes Prepared Using Supercritical Carbon Dioxide

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mauro Banchero ◽  
Silvia Ronchetti ◽  
Luigi Manna
Keyword(s):  
Dissolution Rate ◽  
Water Solubility ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Pharmaceutical Formulations ◽  
Drug Dissolution ◽  
Scanning Calorimetry ◽  
Supercritical Treatment ◽  
The Fourier Transform

Complexes of methyl-β-cyclodextrin and ketoprofen, a crystalline anti-inflammatory drug with poor water solubility, have been prepared for the first time in the presence of supercritical CO2at 40°C and 20 MPa. The supercritical treatment allows these pharmaceutical formulations to be prepared without the use of any auxiliary agents or organic solvents. The treated samples were characterized through differential scanning calorimetry, X-ray diffractometry, and the Fourier transform infrared spectroscopy to exclude the presence of crystalline drug and check the formation of the complexes. The increase of the drug dissolution rate was investigated performing in vitro release tests in aqueous solutions. The results showed that the supercritical treatment can be an efficient method to obtain inclusion complexes with enhanced release kinetics. The operating methods of the release tests, that is, the “tablet method” or the “dispersed amount method,” affected both the dissolution rate and its dependence on the drug amount in the samples. On the contrary, the variation of the pH of the dissolution medium did not show any effect on the release rate of the supercritical complexes.

In Vitro Release Characteristics of Hydrophobic Breast Cancer Drug Loaded Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles

2015 ◽  
Vol 1123 ◽  
pp. 312-315 ◽  
Author(s):  
Akhtar Jahan Siddiqa ◽  
Koel Chaudhury ◽  
Basudam Adhikari
Keyword(s):  
Breast Cancer ◽  
Controlled Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Extended Period ◽  
Plga Nanoparticles ◽  
Cancer Drug ◽  
Physiological Fluid ◽  
Polymer Ratio

The present work focuses on the development of biodegradable PLGA nanoparticles (NPs) for controlled release of a breast cancer drug, letrozole. NPs of different drug-polymer ratio formulations (F1, F2, F3, F4) were fabricated using solvent evaporation technique. Physico-chemical characteristics of these NPs were assessed using dynamic light scattering (DLS) spectrophotometer. In-vitro drug release study was carried out over an extended period of 30 days at 37 °C in simulated physiological fluid. To evaluate the release kinetics, data was fitted to different models. NPs with various sizes and size distributions were obtained by altering the drug-polymer ratio. Zeta potential of PLGA and drug loaded NPs were found to be-29.4± 1.3 mV and-21.0±0.6 mV, respectively. The release kinetics of the drug from NPs was in good agreement with Korsmeyer-Peppas model, ensuring controlled release of the drug from the NPs. In-vitro release studies showed high correlation coefficient (R2 = 0.90) for formulation F2 and F3 up to 30 days. It is concluded that NPs with F2 and F3 formulations provide a controlled release of the incorporated drug and, therefore, hold promise to be investigated further in detail.

scholarly journals Enhancement of the dissolution profile of the diuretic hydrochlorothiazide by elaboration of microspheres

2018 ◽  
Vol 83 (11) ◽  
pp. 1243-1259
Author(s):  
Oum Larbi ◽  
Haouaria Merine ◽  
Youssef Ramli ◽  
Fawzia Toumi ◽  
Kaddour Guemra ◽  
...  
Keyword(s):  
Ftir Spectroscopy ◽  
Release Kinetics ◽  
Drug Loading ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Xrd Analysis ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Scanning Calorimetry

Hydrochlorothiazide (HCTZ), which was developed and introduced in the late 1950s, is still one of the most frequently employed drugs in antihypertensive treatments. Its poor aqueous solubility is one of the reasons for its limited bioavailability after oral administration. The present paper provides details of the preparation of HCTZ-loaded microspheres by the solvent evaporation technique. A total of seven formulations were prepared using ethyl cellulose, poly(?-caprolactone) (PCL), ?-cyclodextrin (?-CD) and synthesized poly-(methyl methacrylate) (PMMA) of different molecular weights in different drug-to-carrier ratios in order to investigate their effect on the encapsulation efficiency and drug release kinetics. The prepared formulations were characterized by Fourier transform-infrared (FTIR) spectroscopy, powder X-ray diffractometry, differential scanning calorimetry, yield, drug loading, optical microscopy, surface morphology by scanning electron microscopy (SEM), and in vitro release studies in simulated gastrointestinal tract fluid. The loading efficiency was found in the range from 18?0.34 to 39?0.95 %. The microspheres were spherical, and the mean Sauter diameter (d32) of the obtained microparticles ranged from 26?0.16 to 107?0.58 ?m. The presence of the drug and polymer carriers in the microparticles was confirmed by FTIR spectroscopy and XRD analysis. In vitro dissolution studies showed that the release rate was largely affected by the characteristics of the microparticles, namely the particle size and the nature of the matrix. The release data are best fitted to the Higuchi model with high correlation coefficients (r?).

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