Stabilization of Deformable Nanovesicles Based on Insulin-Phospholipid Complex by Freeze-Drying

Deformable nanovesicles have been extensively investigated due to their excellent ability to penetrate biological barriers. However, suffering from serious physical and chemical instabilities, the wide use of deformable nanovesicles in medical applications is still limited. Moreover, far less work has been done to pursue the lyophilization of deformable nanovesicles. Here, we aimed to obtain stable deformable nanovesicles via freeze-drying technology and to uncover the underlying protection mechanisms. Firstly, the density of nanovesicles before freeze-drying, the effect of different kinds of cryoprotectants, and the types of different reconstituted solvents after lyophilization were investigated in detail to obtain stable deformable nanovesicles based on insulin-phospholipid complex (IPC-DNVs). To further investigate the underlying protection mechanisms, we performed a variety of analyses. We found that deformable nanovesicles at a low density containing 8% lactose and trehalose in a ratio of 1:4 (8%-L-T) have a spherical shape, smooth surface morphology in the lyophilized state, a whorl-like structure, high entrapment efficiency, and deformability after reconstitution. Importantly, the integrity of IPC, as well as the secondary structure of insulin, were well protected. Accelerated stability studies demonstrated that 8%-L-T remained highly stable during storage for 6 months at 25 °C. Based on in vivo results, lyophilized IPC-DNVs retained their bioactivity and had good efficacy. Given the convenience of preparation and long term stability, the use of combined cryoprotectants in a proper ratio to protect stable nanovesicles indicates strong potential for industrial production.

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Nanosuspension as an Efficient Carrier for Improved Ocular Permeation of Voriconazole

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021999200820154918 ◽

2020 ◽

Vol 21 ◽

Author(s):

Tang Qin ◽

Zhu Dai ◽

Xiaodi Xu ◽

Zilin Zhang ◽

Xiangyu You ◽

...

Keyword(s):

Physical Stability ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Antifungal Drugs ◽

In Vivo Experiments ◽

Transmission Electron ◽

Solvent Evaporation Process ◽

High Entrapment Efficiency

Background: The present limitations related to the ocular administration of antifungal drugs for the treatment of fungal keratitis include poor ocular bioavailability, limited retention time, and low ocular tissues penetration. Methods: This study aimed to prepare a novel ophthalmic voriconazole-loaded nanosuspension based on Eudragit RS 100. Pharmasolve® was explored as a corneal permeation enhancer in voriconazole ophthalmic formulation using in vitro and in vivo experiments. Briefly, 1% voriconazole-loaded nanosuspension was prepared using the quasi-emulsion solvent evaporation process. Results: Characterizations of the voriconazole-loaded nanosuspension by Zetasizer Nano ZS and transmission electron microscope (TEM) showed a uniform spherical shape without any agglomeration. The well-discreted nanoparticle with size of 138 ± 1.3 nm was achieved with high entrapment efficiency (98.6 ± 2.5 %) and a positive zeta potential in the range of 22.5 - 31.2 mV, indicating excellent physical stability. Discussion: Voriconazole-loaded nanosuspension containing the penetration enhancer displayed good permeability both in vitro and in vivocompared with the commercial voriconazole injection. The voriconazole-loaded nanosuspension exhibited good antifungal activity, significantly inhibiting the growth of Candida albicans at a lower concentrations of voriconazole (2.5 μg/mL, p < 0.05). Conclusion: In conclusion, the voriconazole-loaded nanosuspension containing Pharmasolve® can be used as an effective ophthalmic formu-lation for the topical ocular delivery of voriconazole.

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ENRICHMENT OF IN VIVO EFFICACY OF CATECHIN RICH EXTRACT WITH THE APPLICATION OF NANOTECHNOLOGY

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.29569 ◽

2018 ◽

Vol 10 (5) ◽

pp. 281

Author(s):

Monika P. ◽

Basavaraj B. V. ◽

Chidambara Murthy K. N. ◽

Ahalya N. ◽

Bharath S.

Keyword(s):

Zeta Potential ◽

Organic Solvents ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Major Elements ◽

Oral Dosage ◽

Biological Efficiency ◽

Evaporation Technique ◽

Selection Of

Objective: The primary goal of this study was to convert a natural catechin-rich extract into nanoparticles by using a biodegradable and non-toxic polymer Eudragit L 100 to address the various biopharmaceutical problems of catechin.Methods: Nanoparticles were prepared by emulsion solvent evaporation technique using Eudragit L 100 in increasing concentration. Optimization of processing conditions like a selection of organic solvents, diluent and surfactant concentrations, drug and polymer ratio and method of drying to increase the biological efficiency were duly attempted. Parameters such as dynamic light scattering, zeta potential, SEM and energy-dispersive X-ray spectroscopy were assessed for the evaluation of nanoparticles.Results: The entrapment efficiency was found to be between 35-45 % with methanol compared to other organic solvents. The zeta potential values of all the formulations were in the range of±30 mV to±60 mV) which confirms moderate to good stability. A rapid or ‘burst’ effect of the drug release in pH 6.8 buffer showing 92 % in the first 30 min which gradually decreased to 52 % by the end of 180 min but in the pH 7.4, the release was found to be moderate. SEM and DLS indicated particles were of spherical shape lying in a nanometer range of 100 to 200 nm with a proportional influence of polymer on the particles size.Conclusion: Nanoformulations were found to be more stable and confirmed the presence of major elements such as carbon and oxygen. The findings collectively indicate that it may be worthwhile to apply nanotechnology for the design of an advanced oral dosage form for an enhanced bioavailability and biological efficacy.

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Preparation and Characterization of Vitamin a Palmitate-Loaded Nanostructured Lipid Carriers as Delivery Systems for Food Products

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.236-238.1818 ◽

2011 ◽

Vol 236-238 ◽

pp. 1818-1823 ◽

Cited By ~ 5

Author(s):

Rong Kong ◽

Qiang Xia ◽

Guang Yu Liu

Keyword(s):

Vitamin A ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Food Products ◽

Storage Conditions ◽

Correlation Spectroscopy ◽

Nanostructured Lipid Carriers ◽

Laser Diffractometry ◽

Physical And Chemical

Vitamin A Palmitate-loaded Nanostructured Lipid Carriers were prepared by High Pressure Homogenization (HPH) technique. The influences of storage conditions such as time and temperature on the physical and chemical storage stability of VAP-NLCs were studied in details. Preparation and physicochemical properties of VAP lipid nanoparticles were investigated using various analytical equipments such as TEM, photon correlation spectroscopy (PCS), laser diffractometry (LD) and ultraviolet spectrophotometer. The respective optimal HPH pressure and cycles were 70MPa and 5 cycles, so VAP-NLC dispersions under the optimized condition gave rise to the entrapment efficiency (EE) of 99.8%, PI of 0.234, mean diameter of 144±1.7 nm (2% VAP loading capacity). In addition, VAP lipid nanoparticle has a distinct spherical shape, its particle sizes were around 60–330 nm according to VAP contents and zeta potential values -18~-23 mV. Furthermore, the pH of VAP-NLC dispersion was near to 7.0. This study showed that VAP-NLC could hopefully be applied for food products.

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Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment

Pharmaceutics ◽

10.3390/pharmaceutics12080736 ◽

2020 ◽

Vol 12 (8) ◽

pp. 736

Author(s):

Sharif Md Abuzar ◽

Eun Jung Park ◽

Yeji Seo ◽

Juseung Lee ◽

Seung Hyuk Baik ◽

...

Keyword(s):

Colorectal Cancer ◽

Drug Release ◽

Entrapment Efficiency ◽

Lag Phase ◽

Burst Release ◽

Sustained Drug Release ◽

Long Acting ◽

High Entrapment Efficiency

Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.

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‘Preparation and characterization of a novel mucoadhesive carvedilol nano-sponge: a promising platform for buccal antihypertensive delivery’

10.21203/rs.3.rs-268464/v1 ◽

2021 ◽

Author(s):

Nahed Mohamed Sallam ◽

Rania Abdel-Basset Sanad ◽

Mahgoub Mohamed Ahmed ◽

EL Sayed Abdu Khafagy ◽

Mamdouh Mostafa Ghorab ◽

...

Keyword(s):

Spherical Shape ◽

Entrapment Efficiency ◽

Heart Tissue ◽

Buccal Delivery ◽

Oxidative Stress Biomarkers ◽

Tissue Quality ◽

Sonication Technique ◽

Pass Metabolism

Abstract Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina pectoris, and heart failure. Oral administration of CRV showed poor bioavailability (25%), which may be due to exposure to the first-pass metabolism. Buccal delivery was used to boost its bioavailability.Methods: In this study carboxymethylcellulose/hydroxypropyl cellulose (CMC/HPC) composite buccal sponge enriched with CRV bilosomes was developed. Bilosomes were prepared using the thin-film hydration-sonication technique by applying a 32 -factorial design.Results: BL9 possessed the highest desirability value (0.861) and therefore, it was chosen as an optimal bilosomes. It exhibited a spherical shape with 217.2 nm, 87.13% entrapment efficiency, and a sustained release of CRV up to 24h. Consecutively, BL9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain a CMC-HPCL9 bilosomal sponge to enhance CRV buccal delivery. Morphological analysis of the prepared sponge with improved swelling showed a porosity of 67.58 percent. The in vivo assessment of rats indicates that the CMC-HPC/BL9 sponge enhances systolic/diastolic blood pressure, lipid profiles, oxidative stress biomarkers, and heart biomarkers with improved heart tissue quality.Conclusion: These results strongly encourage the use of this novel CMC-HPC/BL9 composite buccal sponge for the management of hypertension.

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Niosome Encapsulation of Curcumin: Characterization and Cytotoxic Effect on Ovarian Cancer Cells

Journal of Nanomaterials ◽

10.1155/2016/6365295 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Ying-Qi Xu ◽

Wen-Rong Chen ◽

Jonathan K. Tsosie ◽

Xi Xie ◽

Peng Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Curcuma Longa ◽

Entrapment Efficiency ◽

Tween 80 ◽

Ovarian Cancer Cells ◽

Clinical Utilization ◽

High Entrapment Efficiency ◽

Low Solubility

Curcumin, a natural chemical compound found in Curcuma longa, has been applied in multiple medicinal areas from antibiotic to antitumor treatment. However, the chemical structure of curcumin results in poor stability, low solubility, and rapid degradation in vivo, hindering its clinical utilization. To address these issues, we have developed a novel niosome system composed of nonionic surfactants: Span 80, Tween 80, and Poloxamer 188. Curcumin was encapsulated in the niosomes with a high entrapment efficiency of 92.3±0.4%. This system provided controlled release of curcumin, thereby improving its therapeutic capability. Dynamic dialysis was conducted to evaluate the in vitro drug release of curcumin-niosomes. Curcumin-niosomes exhibited enhanced cytotoxic activity and apoptotic rate against ovarian cancer A2780 cells compared with freely dispersed curcumin. These results demonstrate that the curcumin-niosome system is a promising strategy for the delivery of curcumin and ovarian cancer therapy.

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Combination of Roll Grinding and High-Pressure Homogenization Can Prepare Stable Bicelles for Drug Delivery

Nanomaterials ◽

10.3390/nano8120998 ◽

2018 ◽

Vol 8 (12) ◽

pp. 998 ◽

Cited By ~ 4

Author(s):

Seira Matsuo ◽

Kenjirou Higashi ◽

Kunikazu Moribe ◽

Shin-ichiro Kimura ◽

Shigeru Itai ◽

...

Keyword(s):

Drug Delivery ◽

High Pressure ◽

Entrapment Efficiency ◽

Molar Ratio ◽

High Pressure Homogenization ◽

Term Stability ◽

Long Term Stability ◽

Long Term Storage ◽

High Entrapment Efficiency

To improve the solubility of the drug nifedipine (NI), NI-encapsulated lipid-based nanoparticles (NI-LNs) have been prepared from neutral hydrogenated soybean phosphatidylcholine and negatively charged dipalmitoylphosphatidylglycerol at a molar ratio of 5/1 using by roll grinding and high-pressure homogenization. The NI-LNs exhibited high entrapment efficiency, long-term stability, and enhanced NI bioavailability. To better understand their structures, cryo transmission electron microscopy and atomic force microscopy were performed in the present study. Imaging from both instruments revealed that the NI-LNs were bicelles. Structures prepared with a different drug (phenytoin) or with phospholipids (dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine) were also bicelles. Long-term storage, freeze-drying, and high-pressure homogenization did not affect the structures; however, different lipid ratios, or the presence of cholesterol, did result in liposomes (5/0) or micelles (0/5) with different physicochemical properties and stabilities. Considering the result of long-term stability, standard NI-LN bicelles (5/1) showed the most long-term stabilities, providing a useful preparation method for stable bicelles for drug delivery.

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Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model

Scientific Reports ◽

10.1038/s41598-019-53996-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Bibhu Prasad Panda ◽

Rachna Krishnamoorthy ◽

Subrat Kumar Bhattamisra ◽

Naveen Kumar Hawala Shivashekaregowda ◽

Low Bin Seng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Drug Delivery ◽

Rat Model ◽

Second Generation ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Poloxamer 188

AbstractDrug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (−18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.

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Preparation and In Vitro-In Vivo Evaluation of Luteolin Loaded Gastroretentive Microsponge for the Eradication of Helicobacter pylori Infections

Pharmaceutics ◽

10.3390/pharmaceutics13122094 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2094

Author(s):

Mohammed Jafar ◽

Mohammed Salahuddin ◽

Mohd Sajjad Ahmad Khan ◽

Yasir Alshehry ◽

Nazar Radwan Alrwaili ◽

...

Keyword(s):

Helicobacter Pylori ◽

Entrapment Efficiency ◽

In Vivo Evaluation ◽

In Vitro Drug Release ◽

Good Production ◽

Sem Study ◽

H Pylori ◽

High Entrapment Efficiency

The current study aimed to develop a luteolin gastric floating microsponge for targeting Helicobacter pylori. The microsponge formulations were prepared by a quasi-emulsion method, and then evaluated for various physicochemical variables. The best microsponge was further assessed for drug-polymer interactions, surface morphology, in vivo floating, and in vitro anti H. pylori activity. The formulation which exhibited comparatively good production yield (64.45% ± 0.83), high entrapment efficiency (67.33% ± 3.79), prolonged in vitro floating time (>8 h), and sustained in-vitro drug release was selected as the best microsponge. The SEM study revealed that the best microsponge was spherical in shape and has a porous surface with interconnecting channels. DSC and XRD studies demonstrated the dispersion of luteolin in the polymeric matrix of the microsponge. Ultrasonography confirmed that the best microsponge could in the rat stomach for 4 h. The in vitro MIC results indicate that the anti H. pylori activity of the best microsponge was almost doubled and more sustained compared to pure luteolin. To conclude, it can be said that the developed luteolin gastric floating microsponge could be a better option to effectively eradicate H. pylori infections and the histopathological and pharmacodynamic assessments of our best microsponge can be expected to provide a rewarding outcome.

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USE OF LACTIC ACID AND SPAN 80 IN THE FORMULATION OF LIPID BASED IMIQUIMOD VESICLES FOR GENITAL WARTS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i2.15915 ◽

2017 ◽

Vol 9 (2) ◽

pp. 292

Author(s):

Saroj Jain ◽

Anupama Diwan ◽

Satish Sardana

Keyword(s):

Particle Size ◽

Lactic Acid ◽

Zeta Potential ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Genital Warts ◽

Formulation Development ◽

Span 80

Objective: The objective of present study was formulation development of imiquimod using lactic acid and span 80 for topical delivery to cure genital warts.Methods: Lipid based vesicles (LBV) of 2% imiquimod were prepared with phospholipoin 90G, ethanol, lactic acid and span 80 using central composite design. The prepared vesicles were optimized statistically and characterized for particle size, zeta potential, percentage entrapment efficiency (% EE) and transmission electron microscopy (TEM). The optimized LBV were incorporated into gel formulation which was evaluated and compared with control gel and marketed formulation.Results: The optimized vesicles had particle size 394.8±9.6 nm, zeta potential-16.5±2.5 mV, % EE 88.27±0.45 and TEM study confirmed the formation of vesicular structure with spherical shape. The gel formulation of imiquimod vesicles showed positive results like spreadability 14.3±0.34 gcm/s, viscosity 13500±1.67 cp, consistency 6.1±0.14 mm and extrudability 16.47±0.11 g/cm2. In vitro permeation amount of drug was remarkably lower (10.13 %) than control (87.17 %) and marketed formulation (27.46 %). Results of retained drug for both in vitro as well as in vivo permeation study and local accumulation efficiency (4.021±0.2292) were considerably higher for LBV gel than control (0.1008±0.002513) and marketed formulation (0.8314±0.0300). To understand the mechanism of interaction between skin and vesicles, fourier transform infra-red spectroscopy studies were also done. Results of skin irritancy test and histological examination revealed biocompatible nature of formulation.Conclusion: Results of in vitro and in vivo studies indicated that this vesicle gel formulation provided efficient and site specific dermal delivery of imiquimod for cure of genital warts.

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