Indinavir-Loaded Nanostructured Lipid Carriers to Brain Drug Delivery: Optimization, Characterization and Neuropharmacokinetic Evaluation

2019 ◽  
Vol 16 (4) ◽  
pp. 341-354 ◽  
Author(s):  
Mohammad Nasiri ◽  
Amir Azadi ◽  
Mohammad Reza Saghatchi Zanjani ◽  
Mehrdad Hamidi
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Zeta Potential ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Free Drug ◽  
Average Particle ◽  
The Brain

Purpose: As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB). Methods: To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a “one-factor-at-a-time” screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study. Result: The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior. Conclusion: As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.

Formulation and evaluation of resveratrol loaded cubosomal nanoformulation for topical delivery

2020 ◽  
Vol 17 ◽  
Author(s):  
Bhaskar Kurangi ◽  
Sunil Jalalpure ◽  
Satveer Jagwani
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Topical Application ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Drug Permeation

Aim: The aim of the study was to formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC) through topical application. Background: Resveratrol (RV) is a nutraceutical compound that has exciting pharmacological potential in different diseases including cancers. Many studies of resveratrol have been reported for anti-melanoma activity. Due to its low bioavailability, the activities of resveratrol are strongly limited. Hence, an approach with nanotechnology has been done to increase its activity through transdermal drug delivery. Objective: To formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC). To evaluate resveratrol-loaded cubosomal gel (RC-Gel) for its topical application. Methods: RC was formulated by homogenization technique and optimized using a 2-factor 3-level factorial design. Formulated RCs were characterized for particle size, zeta potential, and entrapment efficiency. Optimized RC was evaluated for in vitro release and stability study. Optimized RC was further formulated into cubosomal gel (RC-Gel) using carbopol and evaluated for drug permeation and deposition. Furthermore, developed RC-Gel was evaluated for its topical application using skin irritancy, toxicity, and in vivo local bioavailability studies. Results: The optimized RC indicated cubic-shaped structure with mean particle size, entrapment efficiency, and zeta potential were 113±2.36 nm, 85.07 ± 0.91%, and -27.40 ± 1.40 mV respectively. In vitro drug release of optimized RC demonstrated biphasic drug release with the diffusion-controlled release of resveratrol (RV) (87.20 ± 2.25%). The RC-Gel demonstrated better drug permeation and deposition in mice skin layers. The composition of RC-Gel has been proved non-irritant to the mice skin. In vivo local bioavailability study depicted the good potential of RC-Gel for skin localization. Conclusion: The RC nanoformulation proposes a promising drug delivery system for melanoma treatment simply through topical application.

scholarly journals Preparation and characterization of domperidone nanoparticles for dissolution improvement

2018 ◽  
Vol 27 (1) ◽  
pp. 39-52
Author(s):  
Mohammed Sabar Al-lami ◽  
Malath H. Oudah ◽  
Firas A. Rahi
Keyword(s):  
Particle Size ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Methyl Cellulose ◽  
Precipitation Method ◽  
Average Particle ◽  
Antisolvent Precipitation ◽  
Stirring Time

This study was carried out to prepare and characterize domperidone nanoparticles to enhance solubility and the release rate. Domperidone is practically insoluble in water and has low and an erratic bioavailability range from 13%-17%. The domperidone nanoparticles were prepared by solvent/antisolvent precipitation method at different polymer:drug ratios of 1:1 and 2:1 using different polymers and grades of poly vinyl pyrolidone, hydroxy propyl methyl cellulose and sodium carboxymethyl cellulose as stabilizers. The effect of polymer type, ratio of polymer:drug, solvent:antisolvent ratio, stirring rate and stirring time on the particle size, were investigated and found to have a significant (p? 0.05) effect on particle size. The best formula was obtained with lowest average particle size of 84.05. This formula was studied for compatibility by FTIR and DSC, surface morphology by FESEM and crystalline state by XRPD. Then domperidone nanoparticles were formulated into a simple capsule dosage form in order to study of the in vitro release of drug from nanoparticles in comparison raw drug and mixture of polymer:drug ratios of 2:1. The release of domperidone from best formula was highly improved with a significant (p? 0.05) increase.

scholarly journals A Novel Sustained Anti-Inflammatory Effect of Atorvastatin—Calcium PLGA Nanoparticles: In Vitro Optimization and In Vivo Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1658
Author(s):  
Dalia H. Abdelkader ◽  
Ahmed Kh. Abosalha ◽  
Mohamed A. Khattab ◽  
Basmah N. Aldosari ◽  
Alanood S. Almurshedi
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
In Vitro Release ◽  
In Vivo Evaluation ◽  
Water Emulsion ◽  
Atorvastatin Calcium ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Atorvastatin Calcium (At-Ca) has pleiotropic effect as anti-inflammatory drug beside its main antihyperlipidemic action. Our study was conducted to modulate the anti-inflammatory effect of At-Ca to be efficiently sustained for longer time. Single oil-water emulsion solvent evaporation technique was used to fabricate At-Ca into polymeric nanoparticles (NPs). In vitro optimization survey was performed on Poly(lactide-co-glycolide) (PLGA) loaded with At-Ca regrading to particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (% EE), surface morphology and in vitro release pattern. In vitro drug-polymers interactions were fully scanned using Fourier-Transform Infrared Spectroscopy (FTIR) and Differential Scanning calorimetry (DSC) proving that the method of fabrication is an optimal strategy maintaining the drug structure with no interaction with polymeric matrix. The optimized formula with particle size (248.2 ± 15.13 nm), PDI (0.126 ± 0.048), zeta potential (−12.41 ± 4.80 mV), % EE (87.63 ± 3.21%), initial burst (39.78 ± 6.74%) and percent cumulative release (83.63 ± 3.71%) was orally administered in Male Sprague–Dawley rats to study the sustained anti-inflammatory effect of At-Ca PLGA NPs after carrageenan induced inflammation. In vivo results demonstrate that AT-Ca NPs has a sustained effect extending for approximately three days. Additionally, the histological examination revealed that the epidermal/dermal layers restore their typical normal cellular alignment with healthy architecture.

scholarly journals Preparation, characterization, and in vitro evaluation of amphiphilic peptide P12 and P12-DOX nanomicelles as antitumor drug carriers

2020 ◽  
Vol 10 ◽  
pp. 184798042091151 ◽  
Author(s):  
Ping Song ◽  
Wuchen Du ◽  
Wanzhen Li ◽  
Longbao Zhu ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Solid Phase ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Drug Carriers ◽  
Average Particle ◽  
Polymer Micelles ◽  
Amphiphilic Peptide

Polymerized polypeptide nanomicelles have attracted much attention as novel drug carriers because of their good biocompatibility and degradability. To prepare doxorubicin (DOX)-loaded nanomicelles, an amphiphilic peptide, FFHFFH-KKGRGD (P12), was synthesized by solid-phase synthesis, and the physicochemical and drug-release properties, as well as the cytotoxicity of the nanomicelles, were evaluated in vitro. The P12-DOX polymer micelles were prepared by dialysis. The morphology and particle size were characterized by transmission electron microscopy and dynamic light scattering. The critical micelle concentration (CMC) of the polymer was determined by the probe method, and the drug-release characteristics of the micelles were studied by dynamic dialysis. The cytotoxicity and uptake of the P12-DOX micelles were evaluated against mouse breast cancer cells (4T1) and human umbilical vein endothelial cells. The peptide polymer micelles containing DOX were uniformly sized and had a spherical core–shell structure with an average particle size of 128.6 nm. The CMC of the polymer was low (0.0357 mg/mL). The in vitro release of DOX from the micelles is slow and is consistent with first-order kinetics. The copolymer micelles of the P12 polypeptide and DOX can be used as nanoscale spherical carriers of hydrophobic drugs and have broad applicability.

Hepatocellular Carcinoma Targeting and Pharmacodynamics of Paclitaxel Nanoliposomes Modified by Glycyrrhetinic Acid and Ferric Tetroxide

2021 ◽  
Vol 21 ◽  
Author(s):  
Ling Zhao ◽  
Leyi Liang ◽  
Mimi Guo ◽  
Ming Li ◽  
Xuesong Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Delivery ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Glycyrrhetinic Acid ◽  
Migration And Invasion ◽  
Average Particle ◽  
Hcc Cells

Aims: Research on developing targeted delivery of anticancer drugs for the treatment of hepatocellular carcinoma (HCC) is ongoing. This study aimed at synthesizing nanoliposomes modified by glycyrrhetinic acid (GA) and ferric tetroxide (Fe3O4) for targeted delivery of paclitaxel for selective and specific therapy of HCC. Objective: During this project, GA and Fe3O4 were used to jointly modify the active targeting and magnetic orientation of paclitaxel nanoliposomes for enhanced targeting of HCC to improve the efficacy, while reducing the systemic toxicity and side effects of the drug. Methods: In this study, liposomes were prepared to utilize a thin film dispersion method, in which the average particle size of GA/Fe3O4-PTX-LP was 148.9 ± 2.3 nm, and the average Zeta potential was -23.2 ± 3 mV. Based on the TEM characterization, GA/Fe3O4-PTX-LP is a closed particle with bilayer membranes. In vitro release assessments of the drug indicated that the release of GA/Fe3O4-PTX-LP was sustained. Results: In vitro cell tests have demonstrated that GA/Fe3O 4-PTX-LP can inhibit the proliferation, affect the morphology, migration and invasion, and interfere with the cycle of HCC cells. Uptake tests have confirmed that GA/Fe3O4-PTX-LP can promote the uptake of the drug in HCC cells. Conclusion: In vivo targeting experiments have shown that GA/Fe3O4-PTX-LP has a strong ability to target tumors. In vivo antitumor assessments have proven that GA/Fe3O4-PTX-LP can inhibit tumor growth without obvious toxicity. This project provides a promising nano-targeted drug delivery system for the treatment of HCC.

scholarly journals OPTIMIZATION AND CHARACTERIZATION OF DOXORUBICIN LOADED SOLID LIPID NANOSUSPENSION FOR NOSE TO BRAIN DELIVERY USING DESIGN EXPERT SOFTWARE

2021 ◽  
pp. 45-57
Author(s):  
VIRAG A. SHAH ◽  
JAYVADAN K. PATEL
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Zeta Potential ◽  
High Speed ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Brain Targeting ◽  
Solid Lipid ◽  
Stirring Time

Objective: The goal of the current study was to investigate the possible use of solid lipid nanosuspension (SLNs) as a drug delivery method to boost doxorubicin (DOX) brain-targeting performance after intranasal (i. n.) administration.  Methods: 33 factorial design was applied for optimization by using lipid concentration, surfactant concentration, and High-speed homogenizer (HSH) stirring time as dependent variables, and their effect was observed on particles size, Polydispersity index (PDI), and entrapment efficiency.  Results: With the composition of Compritol® 888 ATO (4.6 % w/v), tween 80 (1.9 % w/v), and HSH stirring time, the optimized formula DOX-SLNs prepared (10 min). Particle size, PDI, zeta potential, entrapment efficiency, percent in vitro release were found to be 167.47±6.09 nm, 0.23±0.02, 24.1 mV, 75.3±2.79, and 89.35±3.27 percent in 24 h, respectively, for optimized formulation (V-O). No major changes in particle size, zeta potential, and entrapping efficiency were found in the stability studies at 4±2 °C (refrigerator) and 25±2 °C/60±5% RH up to 3 mo.  Conclusion: Following the non-invasive nose-to-brain drug delivery, which is a promising therapeutic strategy, the positive findings confirmed the current optimized DOX-loaded SLNs formulation.

scholarly journals Design of a Reversible Cholinesterase Inhibitor Mamentine HCL Nanogel: Formulation and In-vitro Evaluation

2021 ◽  
pp. 352-359
Author(s):  
Subhasri Mohapatra ◽  
Sourabh Jain ◽  
Karunakar Shukla
Keyword(s):  
Particle Size ◽  
Cholinesterase Inhibitor ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Storage Period ◽  
Spherical Particles ◽  
Average Particle ◽  
In Situ Gel

Memantine hydrochloride is a is a reversible cholinesterase inhibitor used in the treatment of Alzheimer’s disease, low-moderate affinity, uncompetitive n-methyl-d-aspartate (NMDA) receptor antagonist, with strong voltage dependency and rapid blocking/unblocking kinetics. The present study was explore the potential of thermosensitive nanogel of mamentine loaded nanoparticle. In situ gel choosing due to restrict unwanted exposure in blood and other healthy tissues, thus eliminate hemolytic side effects of the drug and offer easy administration in vivo. Nanoparticle prepared by ionic gelation method and further the dried nanoparticle incorporates with in situ gel.  The in situ gel prepared by cold method using the solutions of Poloxamer-188 and Carbopol-934. The Transmission electron microscopy showed the spherical particles  with  smooth surface which was in conformity  with the SEM and Zetasizer  data for particle size. The pH of the formulations was found to be satisfactory and was in the range of 6.8±0.039 -7.4±0.053 and also mucoadhesive strength was show in table. The mucoadhesive strength of all formulations was varies from 2398±0.0004 to 4945±0.0002 dynes/cm2. In-vitro diffusion study of the in situ gel (N1-N8) was performed using modified Franz diffusion cell with dialysis membrane in phosphate buffer pH 6.5 for a period of 24 hours. The in vitro release study were fitted into various kinetic models viz zero order, first order, higuchi model and korsmeyer peppas equation. Stability studies for optimized formulations were carried out at 4.0 ± 0.5°C and 37 ± 0.5ºC for a period of four weeks. There was no significant variation found in physical appearance, average particle size and % drug content of the in situ nanogel N2. No visible changes in the appearance of the gel formulation were observed at the end of the storage period.

Synthesis and Characterization of Alginate-Based Hydrogel Microbeads for Magnesium Release

2016 ◽  
Author(s):  
Shalil Khanal ◽  
Udhab Adhikari ◽  
Nava P. Rijal ◽  
Devdas Pai ◽  
Jagannathan Sankar ◽  
...  
Keyword(s):  
Particle Size ◽  
Tissue Injury ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Synthesis And Characterization ◽  
Average Particle ◽  
Release Study ◽  
Vitro Release

Magnesium injection is a suitable approach for replenishment of its ions (Mg++) during neural or tissue injury and stroke to avoids risks associated with abnormally low level of Mg++ in blood. In this study, alginate encapsulated magnesium sulfate microbeads were fabricated by the electrospraying technique for Mg++ delivery. Microbeads were evaluated for particle size and surface morphology using inverted optical microscopy and scanning electron microscopy (SEM) respectively. Average particle size of 200–500 μm for hydrated and 50–200 μm for dry beads were observed. An in vitro release study of Mg++ was performed; revealing a cumulative release of ∼50% within first 24 h. This strategy can potentially be useful for the targeted local delivery of magnesium at required concentrations and subsequently enhance the therapeutic efficacy of magnesium in treating tissue injury or stroke.

scholarly journals Preparation and Characterization of Chitosan Coated PLGA Nanoparticles of Resveratrol: Improved Stability, Antioxidant and Apoptotic Activities in H1299 Lung Cancer Cells

Coatings ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 439 ◽  
Author(s):  
Hibah M. Aldawsari ◽  
Nabil A. Alhakamy ◽  
Rayees Padder ◽  
Mohammad Husain ◽  
Shadab Md
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Average Particle Size ◽  
Spherical Shape ◽  
Entrapment Efficiency ◽  
Aqueous Solubility ◽  
Plga Nanoparticles ◽  
Steady Increase ◽  
Average Particle

Resveratrol (RES) is a polyphenolic compound which has shown beneficial pharmacological effects such as anti-inflammatory, antioxidant, and anti-cancer effects. However, poor aqueous solubility, bioavailability, and low stability are the major limitations to the clinical application of RES. Therefore, in the present study, chitosan (CS) coated PLGA nanoparticles of RES (CS-RES-PLGA NPs) was developed, characterized and its anticancer activity was evaluated in the H1299 lung carcinoma cell line. The effects of the increase in CS coating and cryoprotectant concentration on particle size, polydispersity index (PDI) and zeta potential (ZP) were determined. The particle size, PDI, ZP and entrapment efficiency of the optimized CS-RES-PLGA NPs were found to be 341.56 ± 7.90 nm, 0.117 ± 0.01, 26.88 ± 2.69 mV and 75.13% ± 1.02% respectively. The average particle size and ZP showed a steady increase with an increase in CS concentration. The increase in positive zeta potential is evident for higher CS concentrations. The effect of trehalose as cryoprotectant on average particle size was decreased significantly (p < 0.05) when it was increased from 1%−5% w/v. TEM and SEM showed uniform particle distribution with a smooth surface and spherical shape. The CS coating provides modulation of in vitro drug release and showed a sustained release pattern. The stability of RES loaded PLGA NPs was improved by CS coating. CS-coated NPs showed greater cytotoxicity and apoptotic activities compared to free RES. The CS coated NPs had a higher antioxidant effect than the free RES. Therefore, CS coated PLGA NPs could be a potential nanocarrier of RES to improve drug solubility, entrapment, sustain release, stability and therapeutic application.

scholarly journals Formulation and Evaluation of Ketoconazole Nanosponge gel

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Vijay R Chakote ◽  
◽  
Ms.Deepali R. Wagh ◽  
Mr. Rahul S. Waghmare ◽  
Umesh T. Jadhao ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Average Particle Size ◽  
In Vitro Release ◽  
Average Particle ◽  
Sustained Drug Release ◽  
Percentage Yield ◽  
Viscosity Study ◽  
Cross Linker

Ketoconazole Nanosponges were prepared by using Hyper cross linked β-cyclodextrin method by using different concentration of cross-linker. Diphenyl carbonate was used as the cross linking polymer. Nanosponge formulations were prepared by using β-CD: cross linker ratios of 1:15, 1:10, 1:5 and 1:3.Thepreparednanosponges were evaluated for percentage yield, incorporation efficiency, particle size, drug polymer compatibility, scanning electron microscopy andin-vitrodrugrelease.SEM studies confirmed their porous structure with number of nano channels. The FTIR spectra showed stable character of Ketoconazole in mixture of polymers and revealed the absence of drug polymer interactions. DSC study revealed that drug was involved in complexation with nanosponges. The average particle size of Ketoconazole nanoparticles was found to be in the range of 78.81± 0.20 nm to336.02 ± 0.124nm.The drug release from nanosponges was found to extended upto 8hr. 82 to 92%.The nano sponges were formulated into gel using Carbopol 940Batches G1 to G4 were prepared by incorporating nanosponges equivalent to 6%w/w of ketoconazole in different polymer concentrations respectively and evaluated for Percent drug content, Viscosity study, Spreadability study, In vitro diffusion studies. Nanosponge gel G1 showed the optimum pH, viscosity, Spread ability and In vitro release. Drug diffusion from the nanosponge loaded gel formulations was show sustained rate. A sustained release topical drug delivery of Ketoconazole developed as a nanosponge loaded gel offers solubilizing matrix for the drug, served as a local depot for sustained drug release and provided a rate limiting matrix barrier for modulation of drug release.

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