Optimization of Hyaluronate-Based Liposomes to Augment the Oral Delivery and the Bioavailability of Berberine

Various perspectives had been utilized to enhance the poor intestinal permeability and bioavailability of drugs with low water solubility. Berberine (Brb) is a unique molecule that possesses multiple therapeutic activities such as antimicrobial, anti-inflammatory, antioxidant and anti-hyperglycemic effects. To improve Brb permeability and bioavailability, this study presents a newly developed formulation, namely Brb hyaluronate-based liposomes, prepared by using film hydration method and characterized by dynamic light scattering measurements, entrapment efficiency percentage (EE%), transmission electron microscope (TEM), in vitro drug release and physical stability. The bioavailability of the selected formulations was assessed in vivo after oral administration to rats. The results revealed an enhanced effect of hyaluronic acid on the entrapment efficiency, reaching 78.1 ± 0.1% with mean size 520.7 ± 19.9 nm. Sustained release of Brb was recorded up to 24 h in comparison to Brb solution. Physical stability was maintained for three months at refrigeration temperature. Results of pharmacokinetics studies indicated the potential of the liposomal formulation to increase the oral bioavailability of Brb and to accelerate its entry into the bloodstream. The obtained results are accredited to the lipophilic nature of the prepared system, resembling the structural features of bio-membrane, in addition to their small size that enhances intestinal penetration.

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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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Development of NIPAAm-PEG acrylate polymeric nanoparticles for co-delivery of paclitaxel with ellagic acid for the treatment of breast cancer

Journal of Polymer Engineering ◽

10.1515/polyeng-2018-0169 ◽

2019 ◽

Vol 39 (3) ◽

pp. 271-278 ◽

Cited By ~ 3

Author(s):

Suruchi Suri ◽

Mohd. Aamir Mirza ◽

Md. Khalid Anwer ◽

Abdullah S. Alshetaili ◽

Saad M. Alshahrani ◽

...

Keyword(s):

Breast Cancer ◽

Particle Size ◽

Ellagic Acid ◽

Oral Delivery ◽

Polymeric Nanoparticles ◽

Entrapment Efficiency ◽

Shell Nanoparticles ◽

Transmission Electron ◽

Core Shell Nanoparticles

Abstract The aim of the current study was to develop a dual-loaded core shell nanoparticles encapsulating paclitaxel (PTX) and ellagic acid (EA) by membrane dialysis method. Based on particle size, polydispersity index (PDI), and entrapment efficiency, the dual drug-loaded nanoparticles (F2) was optimized. The optimized nanoparticles (F2) showed a particle size of 140±2 nm and a PDI of 0.23±3. The size and the morphology were confirmed by transmission electron microscopy (TEM) and found agreement with the results of dynamic light scattering. The entrapment efficiencies of total drug (PTX and EA), PTX, and EA in the nanoparticles (F2) were measured as 80%, 62.3%, and 37.7%, respectively. The in vitro release profile showed a controlled release pattern for 48 h. A higher cytotoxicity was observed with nanoparticles (F2) in comparison to free PTX. The results revealed that co-delivery of PTX and EA could be used for its oral delivery for the effective treatment of breast cancer.

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BENAZEPRIL HYDROCHLORIDE LOADED NIOSOMAL FORMULATION FOR ORAL DELIVERY: FORMULATION AND CHARACTERIZATION

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.27564 ◽

2018 ◽

Vol 10 (5) ◽

pp. 66

Author(s):

Ameerah A. Radhi

Keyword(s):

Zeta Potential ◽

Oral Delivery ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Potential Range ◽

Transmission Electron ◽

Study Results ◽

Span 60 ◽

A Charge

Objective: The objective of the present study was to formulate niosomal formulations of benazepril hydrochloride in an attempt to overcome the hurdles associated with itʼs poor oral absorption.Methods: Nine formulations were prepared with various ratios of sorbitan monostearate (span 60), sorbitan monopalmitate (span 40) and polyoxyethylene 2 stearyl ether (brij 72) as non-ionic surfactants, cholesterol as a stabilizing agent and soya lecithin as a charge imparting agent. Then, they were characterized for vesicle size, polydispersity (PDI), entrapment efficiency (EE %), release profile, zeta (ζ) potential and transmission electron microscopy (TEM).Results: Niosomal formulations exhibited an efficient entrapment range between (80.4-97.8) percent, vesicles size analyses revealed the formation of homogenously dispersed vesicles having a size range of (3.9±1.7-8.72±4.4) micrometers. The in vitro release studies revealed that all formulations displayed sustained release in comparison with the pure drug. Formulations prepared with span 60 and span 40 possessed adequate stability according to zeta potential analysis, whereas brij 72 failed the test and possessed inadequate zeta potential range. TEM images of the optimized formulations (F7 and F8) have confirmed the formation of vesicles with spherical shapes.Conclusion: Based on the study results, niosomal formulations seem to be attractive alternatives to conventional delivery for benazepril hydrochloride.

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β-Sitosterol Loaded Nanostructured Lipid Carrier: Physical and Oxidative Stability, In Vitro Simulated Digestion and Hypocholesterolemic Activity

Pharmaceutics ◽

10.3390/pharmaceutics12040386 ◽

2020 ◽

Vol 12 (4) ◽

pp. 386

Author(s):

Yasamin Soleimanian ◽

Sayed Amir Hossein Goli ◽

Jaleh Varshosaz ◽

Lorenzo Di Cesare Mannelli ◽

Carla Ghelardini ◽

...

Keyword(s):

Oxidative Stability ◽

Oral Delivery ◽

Physical Stability ◽

Density Lipoprotein ◽

Water Soluble ◽

Nanostructured Lipid Carrier ◽

Lipid Mixture ◽

Simulated Digestion

The objective of the present study was to explore the potential of nanostructured lipid carriers (NLCs) for improving the oral delivery of β-sitosterol, a poorly water-soluble bioactive component with hypocholesterolemic activity. Two β-sitosterol formulations with different solid lipid compositions were prepared by melt emulsification, followed by the sonication technique, and the effect of storage conditions and simulated digestion on the physical, chemical and oxidative stability, bioaccessibility and release were extensively studied. Both NLC preparations remained relatively stable during the four weeks of storage at different conditions (4, 25 and 40 °C), with more superior stability at lower temperatures. The in vitro digestion experiment indicated a high physical stability after exposure to the simulated mouth and stomach stages and an improved overall β-sitosterol bioaccessibility at the end of the digestion. The NLCs presented an increased solubility and gradual release which could be justified by the remarkable affinity of β-sitosterol to the complex lipid mixture. An in vivo study demonstrated an improved reduction in the total cholesterol and low-density lipoprotein cholesterol plasma levels in mice compared with the drug suspension. These investigations evidenced the potential of the developed NLC formulations for the enhancement of solubility and in vivo performance of β-sitosterol.

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Topical Delivery of Apremilast Loaded Nanostructured Lipid Carrier Based Hydrogel for Psoriasis Therapy

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i28b31531 ◽

2021 ◽

pp. 7-20

Author(s):

S. M. Sindhoor ◽

Marina Koland

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Extended Release ◽

Ex Vivo ◽

Entrapment Efficiency ◽

Transmission Electron ◽

Psoriasis Therapy ◽

Systemic Side Effects

Background: Apremilast (APR) is an orally administered selective phosphodiesterase 4 inhibitor approved to treat plaque psoriasis and psoriatic arthritis and is available as an oral tablet formulation. However, its systemic side effects limit its application. The low solubility and permeability of apremilast make it difficult to administer it through the skin. Hence an attempt is made to incorporate apremilast into a suitable nanocarrier to facilitate its topical delivery. Aims: To formulate and characterize Apremilast loaded nanostructured lipid carriers for the management of psoriasis to reduce the systemic side effects. Methodology: Apremilast loaded Nanostructured Lipid carriers (NLC) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Sefsol 218, Tween 80 and Transcutol P as Solid Lipid, Liquid lipid, Surfactant and Penetration Enhancer. The NLC was incorporated into carbapol 934 dispersion to convert it into a gel. The NLC formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the NLC gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, Skin deposition and In vivo studies. Results: The formulated Apremilast loaded showed particle size of less than 200 nm (i.e.170.32nm) with a narrow PDI of 0.267. Entrapment efficiency revealed that 89.26±01.22% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the nanocarrier. The extended-release pattern of the formulated NLC for 24h was observed in the in vitro release studies and followed the Higuchi model(R2=0.9966). Ex vivo permeability showed a 6.14 fold increase in permeability and 74.05±0.25% deposition of apremilast loaded NLC gel compared to apremilast gel. The formulation was stable for three months without significant changes. In vivo skin studies showed that the prepared NLC did not have any skin irritation potential. The antipsoriatic activity demonstrated by the Apremilast loaded NLC gel in the imiquimod induced psoriasis model in mice was comparable to the standard treatment. Conclusion: Apremilast loaded NLC demonstrated enhanced permeation, improved skin retention and extended-release compared to conventional gel. The developed formulation can be an alternative for psoriasis therapy after clinical trials in the future.

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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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Lutein encapsulated oleic - linoleic acid nanoemulsion boosts oral bioavailability of retinal protective carotenoid lutein in rat model

10.21203/rs.3.rs-413208/v1 ◽

2021 ◽

Author(s):

Veeresh B Toragall ◽

Twinkle Godhwani ◽

V Baskaran ◽

Naveen Jayapala

Keyword(s):

Linoleic Acid ◽

Oral Bioavailability ◽

Mixed Micelles ◽

Water Solubility ◽

Health Benefits ◽

Aqueous Solubility ◽

Mean Size ◽

The Mean

Abstract There is excessive interest in emerging colloidal delivery systems to enhance the water solubility and oral bioavailability of lutein, which is a hydrophobic carotenoid claimed to possess health benefits. The present study aimed to design lutein-enriched nanoemulsions with improved physicochemical properties and to achieve various health benefits of lutein. The prepared lutein nanoemulsion was characterized, and its bioavailability was examined in vitro (simulated gastrointestinal digestion) and in vivo. The mean size, PDI and zeta potential of the lutein nanoemulsion were 110 ± 8 nm, 0.271 and 36 ± 2 mV, respectively. Furthermore, TEM examination revealed that the particles are nanosized and spherical in shape. Notably, the aqueous solubility of the nanoemulsion was 726-fold higher than that of free lutein. The composite nanoemulsion also showed exceptionally higher (87.4%) in vitro bioaccessibility than that of nonencapsulated or free lutein (15%). The in vivo bioavailability of lutein nanoemulsion (112.6 ng/mL) was much higher than that of nonencapsulated lutein (48.6 ng/ml) and mixed micelles (68.5 ng/mL), and the tissue distribution pattern of lutein nanoemulsion showed higher lutein accumulation in the liver (2.80- and 1.70-fold) and eye (1.91- and 1.48-fold) compared to free lutein and mixed micelle-fed groups. These results suggested that oleic acid-linoleic acid composite nanoemulsions may be a promising delivery system for lutein and may help enhance the solubility, oral bioavailability and bioefficacy of lutein and could be used as an ingredient for the formulation of beverages or functional foods.

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Development of Polymeric Nanocarriers for Brain Targeted Delivery of Atorvastatin: A Quality-By-Design Approach

Drug Delivery Letters ◽

10.2174/2210303109666191202102517 ◽

2020 ◽

Vol 10 (2) ◽

pp. 149-158

Author(s):

Guilherme A.G. Martins ◽

Fabio S. Murakami ◽

Mauro S. Oliveira ◽

Ana F. Furian ◽

Helen Treichel ◽

...

Keyword(s):

Quality By Design ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Physicochemical Characteristics ◽

In Vivo Studies ◽

Mean Size ◽

Release Study ◽

Vitro Release

Objective: Atorvastatin (ATV) is effective in reducing total cholesterol and low-density lipoprotein levels. Furthermore, it produces pleiotropic effects in neurodegenerative conditions such as Parkinson's, Alzheimer's, and epilepsy. However, due to the effective defense system of the central nervous system (CNS), the development of new medicines for clinical conditions has proven difficult. In this context, nanotechnology was applied as a promising solution to promote drug vectorization to the brain. Methods: The solvent emulsification-diffusion method was used to develop nanoparticles (NPs) based on polylactic acid and coated with polysorbate 80 containing ATV. Quality-by-Design (QbD) was used in the optimization of nanoparticles production through the application of the experimental design Box-Behnken Design. Results: After optimizing the independent factors including sonication time, surfactant concentration and surfactant volume, the NPs presented physicochemical characteristics such as entrapment efficiency of 86.4 ± 2.4%, mean size of 225.2 ± 4.8 nm, and zeta potential of -14.4 ± 0.36 mV. In the in vitro release study, approximately 20% of the encapsulated ATV was released. Conclusion: The application of QbD was very useful in demonstrating its applicability in the nanotechnological pharmaceutical area for controlling and predicting the influence of the variables in the production of NPs. The NPs developed in this study presented adequate physicochemical characteristics, which is promising for future in vivo studies. The physicochemical characteristics included entrapment efficiency of 86.4 ± 2.4%, mean size of 225.2 ± 4.8 nm, and zeta potential of -14.4 ± 0.36 mV. In the in vitro release study, approximately 20% of the encapsulated ATV was released. The application of QbD was very useful in demonstrating its applicability in the nanotechnological pharmaceutical area for controlling and predicting the influence of the variables in the production of NPs. The NPs developed in this study presented adequate physicochemical characteristics, which is promising for future in vivo studies.

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CUR-CA-THIONE: A NOVEL CURCUMIN CONCOCTION WITH ENHANCED WATER SOLUBILITY AND BRAIN BIO-AVAILABILITY

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.15093 ◽

2016 ◽

Vol 8 (12) ◽

pp. 265 ◽

Cited By ~ 1

Author(s):

Devang Y. Shelat ◽

Sanjeev R Acharya

Keyword(s):

Wistar Rats ◽

Water Solubility ◽

Release Kinetics ◽

Entrapment Efficiency ◽

Systemic Circulation ◽

Oral Route ◽

Male Wistar Rats ◽

Dialysis Bag

Objective: Curcumin, is widely studied as a potential drug in treating various disorders but lacks applicability due to poor water solubility and tissue bioavailability. The main objective of the study was to develop a formulation of curcumin that has enhanced water solubility and brain bioavailability.Methods: A curcumin concoction was prepared using solvent evaporation technique taking casein and glutathione as vectors. Various process parameters were identified namely time, temperature, pH and vector while formulation parameters included drug entrapment, anti-oxidant activity, and water solubility. The concoctions were evaluated for in vitro release kinetics at three pH i.e. 1.2, 4.5 and 6.2 at six-time intervals i.e. 10, 20, 30, 40, 60, 120 min using dialysis bag membrane. The same kinetics was further validated using same time points with wistar rats and giving concoction at a single dose of 2 g/kg via the oral route.Results: A concoction i.e. CUR-CA-THIONE having significant entrapment efficiency (77.83%, 97.75%, 90.19%), water solubility (40, 350 and 45 times than normal curcumin) and DPPH activity (IC50: 28.91, 25.07 and 27.89) was evaluated in concoctions CUR-CA-THIONE-T.1, CUR-CA-THIONE-T.2 and CUR-CA-THIONE-T.3 respectively. These formulations were then carried out for in vitro release profile at different pH with average release obtained between 20-30 min. In vivo kinetics was studied by isolating tissues like brain, liver, lung, kidney and spleen in male wistar rats and maximum brain bioavailability was observed for CUR-CA-THIONE-T.3 at 30 min with 75 ng/g of brain tissue.Conclusion: The experiment helps in concluding that CUR-CA-THIONE has improved its water solubility and is able to by-pass systemic circulation to targeted activity.

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Nanoparticles made of multi-block copolymer of lactic acid and ethylene glycol containing periodic side-chain carboxyl groups for oral delivery of cyclosporine A

Journal of The Royal Society Interface ◽

10.1098/rsif.2010.0046.focus ◽

2010 ◽

Vol 7 (suppl_4) ◽

Cited By ~ 16

Author(s):

D. D. Ankola ◽

A. Battisti ◽

R. Solaro ◽

M. N. V. Ravi Kumar

Keyword(s):

Molecular Weight ◽

Particle Size ◽

Lactic Acid ◽

Block Copolymer ◽

Ethylene Glycol ◽

Cyclosporine A ◽

Oral Delivery ◽

Entrapment Efficiency

The purpose of this study was to evaluate the potential of new carboxylated multi-block copolymer of lactic acid and ethylene glycol (EL14) for nanoparticle (NP) formation and their ability to deliver high molecular weight hydrophobic drug—cyclosporine A (CsA). CsA-loaded EL14 NPs were compared with traditional poly(lactide-co-glycolide) (PLGA) NPs, both prepared by emulsion–diffusion–evaporation process. On the one hand, the increase in drug payload from 10 to 30 per cent for EL14 NPs showed no difference in particle size, however the entrapment efficiency tends to decrease from 50 to 43 per cent; on the other hand, the more hydrophobic PLGA showed an increasing trend in entrapment efficiency from 20 to 62 per cent with increasing particle size. Over 90 per cent of CsA was released in vitro from both the nanoparticulates; however, the release was much slower in the case of more hydrophobic PLGA. On in vivo evaluation in rats, the NPs made of EL14 showed a higher C max , a faster T max and enhanced tissue levels to that of PLGA that are crucial for CsA's activity and toxicity; however, the overall bioavailability of the nanoparticulates was similar and higher than Neoral. Together these data demonstrate the feasibility of NPs made of low molecular weight, hydrophilic polymer EL14 for efficient delivery of CsA.

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