Polyamidoamine-Remdesivir Conjugate: Physical Stability and Cellular Uptake Enhancement

Nucleoside analogue antiviral remdesivir works by inhibiting the RNA-dependent RNA polymerase enzyme and terminating the viral replication. Currently, remdesivir is under a clinical trial for its activity against SARS-CoV-2. In the blood, remdesivir will undergo an enzymatic reaction to become monophosphate analogue form which is difficult to penetrate into the cell membrane. PAMAM (polyamidoamine) dendrimer is a good carrier to encapsulate remdesivir as a water-insoluble drug (0,339 mg/mL). Entrapment of remdesivir in the PAMAM cavity avoided remdesivir molecules to not undergo the enzymatic reactions. This study aimed to synthesize, characterize and evaluate cellular uptake of PAMAM-Remdesivir conjugate. PAMAM-Remdesivir was prepared with various stirring times (3, 6, 12, 24, and 48 hours). The conjugates were characterized to observe the size and particle distribution using Particle Size Analyzer, encapsulating efficiency using UV-Vis Spectroscopy, interaction between PAMAM and remdesivir particle using Fourier Transform Infrared Spectroscopy and cellular uptake of PAMAM-RDV using Fluorescence Microscope. The optimized stirring time of PAMAM-Remdesivir conjugate was 24 hours wich resulted the particles charge of + 23,07 mV of zeta potential, 1008 nm of particle size, 0,730 of PDI, and 69% entrapment efficiency. In addition, the FTIR analysis showed that remdesivir molecules successfully conjugated to PAMAM. Thus, through strring optimization time, the remdesivir molecules were successfully entrapped to PAMAM cavity. The cellular uptake in Vero Cell of PAMAM-RDV conjugated fluorescein isothiocyanate was observed with fluorescence microscope and had a stronger intensity than remdesivir only solution.

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Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer

Scientific Reports ◽

10.1038/s41598-021-99756-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mahitab Bayoumi ◽

Mona G. Arafa ◽

Maha Nasr ◽

Omaima A. Sammour

Keyword(s):

Particle Size ◽

Skin Cancer ◽

Zeta Potential ◽

Ex Vivo ◽

Physical Stability ◽

Entrapment Efficiency ◽

Penetration Enhancer ◽

Oxidative Stress Biomarkers ◽

Skin Deposition

AbstractSkin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.

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Evaluation of the Physical Stability of Nanostructured Lipid Carrier (NLC) Meloxicam Before and After Strorage 40 Days

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v8i2.13876 ◽

2018 ◽

Vol 8 (2) ◽

Author(s):

Rahmi Annisa ◽

Dewi Melani ◽

Esti Hendradi

Keyword(s):

Particle Size ◽

Ph Value ◽

Physical Stability ◽

Particle Morphology ◽

Entrapment Efficiency ◽

Nanostructured Lipid Carrier ◽

Measurement Results ◽

Before And After ◽

Value Range ◽

Efficiency Test

Objective: The aims this study was to determine the effect of lipid ratio Monostearin and Miglyol 808 roomates gives the physical stability after storage 40 days. Methods: The NLC making was done by using emulsification method in the formation of NLC meloxicam, 3 different lipid ratios were used, including ratios of 6: 4, 7: 3, 8: 2. Results: NLC meloxicam physical stability of the pH, viscosity, particle size, particle morphology and entrapment efficiency. NLC meloxicam belongs to semisolid preparations with pH value range of 5.72-5.87. Increasing viscosity of NLC system is caused by the increase of solid lipid. The measurement results of particle size of three different lipid formulas indicated that the lipid particle size was less than 1000 nm. Entrapment efficiency test of all NLC-lipid compositions revealed quite high result (> 80%). Conclusion: The system uses lipid monostearin NLC meloxicam and Miglyol 808 at a ratio of 8: 2 is the most optimal combination shows physical stability after storage 40 days.

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

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2021v13i5.41137 ◽

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.

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FORMULATION AND OPTIMIZATION OF NIFEDIPINE LOADED NANOCARRIERS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i5.42050 ◽

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

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OPTIMIZATION OF STIRRING SPEED AND STIRRING TIME TOWARD NANOPARTICLE SIZE OF CHITOSAN-SIAM CITRUS PEEL (Citrus nobilis L.var Microcarpa) 70% ETHANOL EXTRACT

Majalah Obat Tradisional ◽

10.22146/tradmedj.24302 ◽

2017 ◽

Vol 22 (1) ◽

pp. 16

Author(s):

Wintari Taurina ◽

Rafika Sari ◽

Uray Cindy Hafinur ◽

Sri Wahdaningsih ◽

Isnindar Isnindar

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Small Particle ◽

Ethanol Extract ◽

Entrapment Efficiency ◽

Ionic Gelation ◽

Small Particle Size ◽

Citrus Peel ◽

West Kalimantan ◽

Stirring Time

Siam citrus peel (Citrus nobilis L. var. Microcarpa) is a plant derived from Sambas Regency, West Kalimantan Province. Bioavailability of herbal active compounds can be enhanced by formulating extract into nanoparticle. The polymer used was chitosan with crosslinker Na-TPP. Stirring speed and stirring time play an important role to produce small particle size in forming nanoparticle using ionic gelation method. Enhancement of stirring speed and stirring time could reduce particle size. Nanoparticles were prepared using ionic gelation method by mixing Na-TPP, extract and chitosan (1:1:6) with varying the stirring speed 500 rpm, 1000 rpm, 1500 rpm and stirring time 1 hrs, 2 hrs, 3 hrs. The particle size of nanoparticle was found to be 85.3 nm at 1000 rpm of stirring speed and 3 hrs of stirring times, with polidispersity index 0.287, zeta potential +32.37 mV and entrapment efficiency 87.12 %.

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Evaluation and Comparison of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Vectors to Develop Hydrochlorothiazide Effective and Safe Pediatric Oral Liquid Formulations

Pharmaceutics ◽

10.3390/pharmaceutics13040437 ◽

2021 ◽

Vol 13 (4) ◽

pp. 437

Author(s):

Paola Mura ◽

Francesca Maestrelli ◽

Mario D’Ambrosio ◽

Cristina Luceri ◽

Marzia Cirri

Keyword(s):

Particle Size ◽

Solid Lipid Nanoparticles ◽

Drug Loading ◽

Physical Stability ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Nanostructured Lipid Carriers ◽

Particle Size Reduction ◽

Solid Lipid ◽

Oral Liquid

The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol® ATO5 and Transcutol® HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire® 44/14 as surfactant rather than PluronicF68 or Tween® 80 yielded a marked particle size reduction (95–75 nm compared to around 600–400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments.

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

10.21203/rs.3.rs-695187/v1 ◽

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.

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COMPARATIVE MUCOPENETRATION ABILITY OF METRONIDAZOLE LOADED CHITOSAN AND PEGYLATED CHITOSAN NANOPARTICLES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i6.17643 ◽

2017 ◽

Vol 10 (6) ◽

pp. 125

Author(s):

Sukhbir Kaur ◽

Chawla V ◽

Narang R K ◽

Aggarwal G

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Chitosan Nanoparticles ◽

Methyl Cellulose ◽

Fluorescein Isothiocyanate ◽

Entrapment Efficiency ◽

Spherical Particles ◽

Detachment Force

Objective: The objective of this study is to compare the mucopenetration ability of metronidazole loaded chitosan (CS) and pegylated CS nanoparticles.Methods: Nanoparticles were prepared by ionic gelation technique using negatively charged pH sensitive polymer, hydroxyl propyl methyl cellulose phthalate with positively charged CS and methoxy polyethylene glycol-grafted-CS (mPEG-g-CS). mPEG-g-CS was synthesized by formaldehyde linkage method and characterized by Fourier transform infrared spectroscopy. The optimized formulations were compared for morphology, particle size, polydispersity index (PDI), entrapment efficiency, bioadhesion detachment force, in vitro and in vivo mucopenetration for CS-mPEG-g-CS nanoparticles.Results: The morphological assessment revealed smooth spherical particles with uniform dispersions. The optimized formulations particle size was found to be 202.7±27 nm and 294.1±46 nm, zeta potential 26.94±2.4 mV and 6.0±1.3 mV. PDI 0.231 and 0.268, entrapment efficiency 79.8±5.4% and 83.6±9.7%, bio-adhesion detachment force 14.98*103 dyne/cm2 and 10.67*103 dynes/cm2, in vitro mucopenetration 78% and 98% for CS-mPEG-g-CS, respectively. The qualitative in vivo mucopenetration result confirms retention of fluorescein isothiocyanate (FITC) labeled mPEG-g-CS nanoparticles till 24 hrs.Conclusion: Nanoparticles with lesser zeta potential and mucoadhesion showed higher mucosal penetration which is evident from FITC labeled histopathological mucus penetration test. Studies thus provided evidence that planned pharmaceutical strategies open new vistas for effective treatment of mucosal infections.

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PHYSICAL STABILITY TESTING OF P-SYNEPHRINE PREPARED AS TRANSFERSOME GEL

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017.v9s1.70_77 ◽

2017 ◽

Vol 9 ◽

pp. 124

Author(s):

Amelia Luthfiah ◽

Erny Sagita ◽

Iskandarsyah Iskandarsyah

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Oral Bioavailability ◽

Lipolytic Activity ◽

Physical Stability ◽

Entrapment Efficiency ◽

Tween 80 ◽

Polydispersity Index ◽

Stability Testing ◽

Span 80

Objectives: While p-synephrine exhibits lipolytic activity, it also has a low oral bioavailability as well as hydrophilic characteristic, so it is difficult forit to penetrate the epidermis if it is made into transdermal preparation. The purpose of this research was to increase the penetration of p-synephrineby preparing it as transfersome gel.Materials and Methods: Three transfersome formulas were prepared—F1, F2, and F3—with the surfactants used at Tween 80, Span 80, and thecombination of Tween 80 and Span 80 with a ratio of 1:1, respectively.Results: The results showed that F1 was the best formula, with the highest entrapment efficiency, of 64.058±0.754%, a particle size average of103.3 nm, polydispersity index 0.269±0.05, and zeta potential of −36.2±0.64 mV, so this formula was employed for the gel formulation. Two gelformulas were then prepared, transfersome gel (GT) and non transfersome gel (GNT).Conclusions: The two gels were evaluated for their physical stability, and GT was found to be more stable than GNT.

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FORMULATION AND EVALUATION OF PHYTOSOME LOTION FROM NOTHOPANAX SCUTELLARIUM LEAF EXTRACT FOR HAIR GROWTH

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i6.42169 ◽

2021 ◽

pp. 178-185

Author(s):

IKA AULIA RAHMI ◽

ABDUL MUN’IM ◽

MAHDI JUFRI

Keyword(s):

Particle Size ◽

Hair Growth ◽

Leaf Extract ◽

Physical Stability ◽

Entrapment Efficiency ◽

Extraction Methods ◽

Microwave Assisted Extraction ◽

Hair Length ◽

Microwave Assisted ◽

Assisted Extraction

Objective: The purpose of this study was to formulate a phytosome lotion from Mangkokan leaf using green solvent extraction. Methods: Ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate, combined with microwave-assisted extraction, was used to obtain flavonoid compounds. Mangkokan leaf extract was formulated into a phytosome with three different ratios of phospholipon (1:0.5), (1:1), and (1:2). Three phytosome formulas were analyzed to identify the best formula. The analysis included morphology, particle size, and zeta potential, entrapment efficiency, and spectrum analysis using an FTIR spectrophotometer. The formula which chosen was formulated into three lotion formulas with different concentration (20%; 25%; 30%) then, evaluated for physical stability, and hair growth activity test included hair length, weight, and diameter. Minoxidil and non-phytosome lotion were used as comparison. Data were analyzed using two-way ANOVA. Results: The FTIR of phytosome was confirmed a complex formation of extract and phospholipon. The phytosome morphology was displayed irregular spherical vesicles. Phytosome with the ratio of phospholipon (1:0.5) was formulated into lotion because has a smaller particle size (289 nm), and higher entrapment efficiency (99.76%±0.24) than others. Phytosome lotions displayed higher activity than 2% minoxidil (p = 0.0001). Phytosome lotion (30%) thus showed the highest efficacy for hair length, weight and diameter. Conclusion: Mangkokan leaf that extracted using 1-butyl-3-methylimidazolium tetrafluoroborate solvent combined with microwave-assisted extraction then formulated into phytosome lotion has higher activity than 2% minoxidil. Lotion that contains 30% mangkokan leaf phytosome was showed the highest efficacy.

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