scholarly journals Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ling-Chun Chen ◽  
Yin-Chen Chen ◽  
Chia-Yu Su ◽  
Wan-Ping Wong ◽  
Ming-Thau Sheu ◽  
...  
Keyword(s):  
Particle Size ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Physical Stability ◽  
Sodium Deoxycholate ◽  
Hydrophobic Core ◽  
Self Assembling ◽  
Human Disorders

Abstract Self-assembling mixed polymeric micelles (saMPMs) were developed for overcoming major obstacles of poor bioavailability (BA) associated with curcumin delivery. Lecithin added was functioned to enlarge the hydrophobic core of MPMs providing greater solubilization capacity. Amphiphilic polymers (sodium deoxycholate [NaDOC], TPGS, CREMOPHOR, or a PLURONIC series) were examined for potentially self-assembling to form MPMs (saMPMs) with the addition of lecithin. Particle size, size distribution, encapsulation efficacy (E.E.), and drug loading (D.L.) of the mixed micelles were optimally studied for their influences on the physical stability and release of encapsulated drugs. Overall, curcumin:lecithin:NaDOC and curcumin:lecithin:PLURONIC P123 in ratios of 2:1:5 and 5:2:20, respectively, were optimally obtained with a particle size of < 200 nm, an E.E. of >80%, and a D.L. of >10%. The formulated system efficiently stabilized curcumin in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C and delayed the in vitro curcumin release. In vivo results further demonstrated that the slow release of curcumin from micelles and prolonged duration increased the curcumin BA followed oral and intravenous administrations in rats. Thus, lecithin-based saMPMs represent an effective curcumin delivery system, and enhancing BA of curcumin can enable its wide applications for treating human disorders.

Optimization of Hydroxypropyl Methylcellulose and Dextrin in Development of Dried Nanosuspension for Poorly Water-Soluble Drug

2020 ◽  
Vol 20 (9) ◽  
pp. 5813-5818
Author(s):  
Eun-Ji Heo ◽  
Sang Yeob Park ◽  
Hye-In Kim ◽  
Ji-Hun Sung ◽  
Hyeok Jin Kwon ◽  
...  
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Oral Absorption ◽  
Drug Loading ◽  
Hydroxypropyl Methylcellulose ◽  
Physical Stability ◽  
Tween 80 ◽  
Water Soluble

The purpose of this study is to identify the effects of a stabilizer and matrix former in the development of a celecoxib dried nanosuspension (DNS) for high dissolution rate and drug loading. Tween 80 and Hydroxypropyl Methylcellulose (HPMC) were used as stabilizers in the bead-milling process and dextrin was used as the matrix former in the spray-drying. Various nanosuspensions (NS) were prepared by varying the ratio of HPMC and dextrin, and the physicochemical properties of each formulation were evaluated for particle size, morphology, drug loading, crystallinity, redispersibility, physical stability and dissolution rate. HPMC efficiently stabilized the NS system and reduced the particle size of NS. The mean particle size of the NS with 0.5% HPMC (w/v) was the smallest (248 nm) of all formulations. Dextrin has been shown to inhibit the increase of particle size efficiently, which is known to occur frequently when NS is being solidified. As the dextrin increased in DNS, the dissolution rates of reconstituted NS were significantly improved. However, it was confirmed that more than the necessary amount of dextrin in DNS reduced the dissolution and drug loading. The dissolution of celecoxib in DNS prepared at the ratio (drug:dextrin, 1:2.5) was almost the highest. The dissolution of optimal formulation was 95.8% at 120 min, which was 2.0-fold higher than that of NS dried without dextrin. In conclusion, these results suggest that the formulation based on Tween 80, HPMC and dextrin may be an effective option for DNS to enhance its in vitro dissolution and in vivo oral absorption.

Anti-Tumor Study of H6, a 4-Substituted Coumarins Derivative, Loaded Biodegradable Self-Assembly Nano-Micelles In Vitro and In Vivo

2019 ◽  
Vol 15 (7) ◽  
pp. 1515-1531 ◽  
Author(s):  
Zejiang Zhu ◽  
Zhengying Su ◽  
Jianhong Yang ◽  
Huili Liu ◽  
Minghai Tang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Therapeutic Window ◽  
Tumor Growth Inhibition ◽  
Mechanism Study ◽  
Tumor Models ◽  
Substituted Coumarins

In our previous study, we identified a class of 4-substituted coumarins as a powerful microtubule inhibitors binding to the colchicine site of β-tubulin. H6 showed potent anti-proliferative ability with IC50 values from 7 to 47 nM, and remarkable ability to reduce tumor growth in several xenograft models including taxol resistant tumor models. However, the extremely hydrophobicity limited its clinical application. In this study, to improve the anticancer activity and reduce the toxicity of H6, we successfully prepared MPEG-PCL with different proportions and H6-loaded polymeric micelles (H6/MPEG2kPCL2k micelles) by a simple thin-film hydration method. The prepared H6/MPEG-PCL micelles had a drug loading of 3.79 ± 0.001%, an encapsulation efficiency of 98.00 ± 0.41%, a mean particle size of 30.45 ± 0.18nm and a polydispersity index (PDI) of 0.096 ± 0.009. Computer simulation results revealed a good compatibility of H6 and MPEG2k-PCL2k copolymer. In in vitro release study and pharmacokinetic study showed H6 micelles can release H6 over an extended period. Furthermore, H6 micelles possessed comparative effect as free H6 in inhibiting cell growth, preventing cell migration, and inducing apoptosis. Mechanism study identified that H6 is a novel reversible microtubule inhibitor. In in vivo studies, H6 micelles exhibited tumor growth inhibition on two pulmonary metastatic tumor models (B16/F10 and 4T1). Importantly, H6 micelles significantly improved the solubility, reduced the toxicity, extended the half-life of drugs, and augmented the therapeutic window. All these results imply that H6 micelles have great potential for suppression of tumor metastasis.

scholarly journals FORMULATION AND OPTIMIZATION OF NIFEDIPINE LOADED NANOCARRIERS

2021 ◽  
pp. 311-317
Author(s):  
ASHWINI JADHAV ◽  
BINOY VARGHESE CHERIYAN
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Physicochemical Characteristics ◽  
Good Choice ◽  
The Stability

Objective: The main aim of this study to formulate a nifedipine-loaded nanocarrier for improving solubility and bioavailability. Methods: To improve the solubility of drug, nifedipine-loaded nanocarrier (lipotomes) were prepared by using the film lipid hydration technique. lipotomes were prepared by using tween 80, which is used for increasing solubility and cetyl alcohol for lipophilic environment. Drug excipients interaction determined by FTIR. lipotomes were characterized for particle size, Entrapment efficiency and zeta potential. lipotomes were optimized by using Design-Expert 12 software. Optimized formula further lyophilized by using different cyroproyectant to improve the stability and oral administration of the drug. Results: FTIR shows there was no interaction between formulation ingredients. Mean particle size, entrapment efficiency, zeta potential was determined and found to be 308.1 nm, 96.7%, 20.1mV, respectively. Surface morphology of lipotomes was observed by a scanning electron microscope (SEM). Optimized lipotomes was lyophilized with Mannitol (8% w/v) was the ideal cryoprotectant to retain the physicochemical characteristics of the OLT formulation after lyophilization. Conclusion: Nifedipine loaded nanocarrier was successfully prepared, using film hydration method. Which have good particle size, EE% and zeta potential. After lyophilization no significant changes was observed in particle size with good physical stability, so it could be a good choice for conventional drug delivery system by doing further investigation as in vitro and in vivo study

scholarly journals Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

2018 ◽  
Vol 19 (10) ◽  
pp. 3132 ◽  
Author(s):  
Liang Li ◽  
Na Liang ◽  
Danfeng Wang ◽  
Pengfei Yan ◽  
Yoshiaki Kawashima ◽  
...  
Keyword(s):  
Folic Acid ◽  
Deoxycholic Acid ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Amorphous State ◽  
Spherical Shape ◽  
Water Soluble ◽  
Proton Nuclear Magnetic Resonance

The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10−3 mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.

scholarly journals Development of Ritonavir Loaded Nanostructured Lipid Carriers Employing Quality By Design (QbD) As A Tool: Characterizations, Permeability, And Bioavailability Studies

2021 ◽  
Author(s):  
Vishal Gurumukhi ◽  
Sanjaykumar Bari
Keyword(s):  
Particle Size ◽  
Quality By Design ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Formulation Development ◽  
Enhanced Solubility ◽  
Formulation Variables

Abstract The objective of the present work was to optimize ritonavir (RTV) loaded nanostructured lipid carriers (NLCs) to improve bioavailability using quality by design (QbD) based technique. Risk assessment was studied using ‘cause and effect’ diagram followed by failure mode effect analysis (FMEA) to identify the effective high-risk variables for the formulation development. Quality target product profile (QTPP) and critical quality attributes (CQAs) were initially assigned for the proposed product. Central composite rotatable design (CCRD) was used to identify the individual and combined interactions of formulation variables. RTV loaded NLC (RTV-NLC) was prepared using emulsification-ultrasonication method. The effect of formulation variables like ultrasound amplitude, lipid concentration, surfactant concentration on their responses like particle size, polydispersity index (PDI), and entrapment efficiency (EE) were studied by CCRD. The optimized formulation was subjected to lyophilization to obtain dry NLCs for solid-state analysis. DSC and PXRD investigations showed RTV was molecularly dispersed in lipid matrix indicating amorphous form present in the formulation. FESEM and AFM depicted the spherical and uniform particles. The enhanced solubility and dissolution may be attributed due to the reduced particle size. The optimized NLCs showed good physical stability during storage for six months. RTV-NLC was further subjected to in vitro studies and found a successful sustained release rate of 92.37±1.03 %. The parallel artificial membrane permeability assay (PAMPA) and everted gut sac model have demonstrated the permeation enhancement of RTV. In vivo study observed the enhanced bioavailability with 2.86 fold suggesting optimized NLC successfully overcome the issue of solubility.

scholarly journals Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Soluplus® Polymeric Micelles Encapsulating Fenbendazole

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1000 ◽  
Author(s):  
Ik Sup Jin ◽  
Min Jeong Jo ◽  
Chun-Woong Park ◽  
Youn Bok Chung ◽  
Jin-Seok Kim ◽  
...  
Keyword(s):  
Polymeric Micelles ◽  
Drug Loading ◽  
Average Particle Size ◽  
A549 Cells ◽  
Pharmacokinetic Studies ◽  
Average Particle ◽  
Severe Toxicity ◽  
Blood Concentrations

Fenbendazole (FEN), a broad-spectrum benzimidazole anthelmintic, suppresses cancer cell growth through various mechanisms but has low solubility and achieves low blood concentrations, which leads to low bioavailability. Solubilizing agents are required to prepare poorly soluble drugs for injections; however, these are toxic. To overcome this problem, we designed and fabricated low-toxicity Soluplus® polymeric micelles encapsulating FEN and conducted toxicity assays in vitro and in vivo. FEN-loaded Soluplus® micelles had an average particle size of 68.3 ± 0.6 nm, a zeta potential of −2.3 ± 0.2 mV, a drug loading of 0.8 ± 0.03%, and an encapsulation efficiency of 85.3 ± 2.9%. MTT and clonogenic assays were performed on A549 cells treated with free FEN and FEN-loaded Soluplus® micelles. The in vitro drug release profile showed that the micelles released FEN more gradually than the solution. Pharmacokinetic studies revealed lower total clearance and volume of distribution and higher area under the curve and plasma concentration at time zero of FEN-loaded Soluplus® micelles than of the FEN solution. The in vivo toxicity assay revealed that FEN-loaded Soluplus® micelle induced no severe toxicity. Therefore, we propose that preclinical and clinical safety and efficacy trials on FEN-loaded Soluplus® micelles would be worthwhile.

scholarly journals Preparation, Biosafety, and Cytotoxicity Studies of a Newly Tumor-Microenvironment-Responsive Biodegradable Mesoporous Silica Nanosystem Based on Multimodal and Synergistic Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Zelai He ◽  
Huijun Zhang ◽  
Hongwei Li ◽  
Yanyan Wang ◽  
Jing Qian ◽  
...  
Keyword(s):  
Particle Size ◽  
Mesoporous Silica ◽  
Tumor Cells ◽  
Blood Compatibility ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Antitumor Effects ◽  
Cytotoxicity Studies

Patients with triple negative breast cancer (TNBC) often suffer relapse, and clinical improvements offered by radiotherapy and chemotherapy are modest. Although targeted therapy and immunotherapy have been a topic of significant research in recent years, scientific developments have not yet translated to significant improvements for patients with TNBC. In view of these current clinical treatment shortcomings, we designed a silica nanosystem (SNS) with Nano-Ag as the core and a complex of MnO2 and doxorubicin (Dox) as the surrounding mesoporous silica shell. This system was coated with anti-PD-L1 to target the PD-L1 receptor, which is highly expressed on the surface of tumor cells. MnO2 itself has been shown to act as chemodynamic therapy (CDT), and Dox is cytotoxic. Thus, the full SNS system presents a multimodal, potentially synergistic strategy for the treatment of TNBC. Given potential interest in the clinical translation of SNS, the biological safety and antitumor activity of SNS were evaluated in a series of studies that included physicochemical characterization, particle stability, blood compatibility, and cytotoxicity. We found that the particle size and zeta potential of SNS were 94.6 nm and -22.1 mV, respectively. Ultraviolet spectrum analysis showed that Nano-Ag, Dox, and MnO2 were successfully loaded into SNS, and the drug loading ratio of Dox was about 10.2%. Stability studies found that the particle size of SNS did not change in different solutions. Hemolysis tests showed that SNS, at levels far exceeding the anticipated physiologic concentrations, did not induce red blood cell lysis. Further in vitro and in vivo experiments found that SNS did not activate platelets or cause coagulopathy and had no significant effects on the total number of blood cells or hepatorenal function. Cytotoxicity experiments suggested that SNS significantly inhibited the growth of tumor cells by damaging cell membranes, increasing intracellular ROS levels, inhibiting the release of TGF-β1 cytokines by macrophages, and inhibiting intracellular protein synthesis. In general, SNS appeared to have favorable biosafety and antitumor effects and may represent an attractive new therapeutic approach for the treatment of TNBC.

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

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

scholarly journals Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1210
Author(s):  
Xieguo Yan ◽  
Shiqiang Wang ◽  
Kaoxiang Sun
Keyword(s):  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
In Vivo Evaluation ◽  
Long Term Treatment ◽  
Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

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