Assessment of a Novel Vitamin D3 Formulation with Nanostructured Lipid Carriers for Transdermal Delivery

2021 ◽  
Vol 18 ◽  
Author(s):  
Laura Junqueira ◽  
Hudson Polonini ◽  
Cristiano Ramos ◽  
Anderson O. Ferreira ◽  
Nádia Raposo ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Vitamin D3 ◽  
Transdermal Delivery ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Nanoparticle Dispersion ◽  
Vitamin D3 Supplementation

Objective: Develop and assess a transdermal emulsion loaded with nanostructured lipid carriers for vitamin D3 supplementation. Methods: Vitamin D3 loaded nanostructured lipid carriers, produced via high shear homogenization and ultrasonication, were assessed for their particle size, distribution, morphology, zeta potential, entrapment efficiency, and cytotoxicity. They were incorporated into a transdermal vehicle, and the stability and ex vivo permeation were evaluated. Results: Spherical nanoparticles were developed with a particle size of 192.5 nm, a polydispersity index of 0.13, a zeta potential of -29.0 mV, and an entrapment efficiency of 99.75%. They were stable (particle size and distribution) for 15 days when stored in a refrigerator and for 30 days at room temperature and 32 °C. The nanoparticles decreased the drug cytotoxicity against fibroblasts, as shown by IC50 (nanoparticle: 32.48 μg mL−1; vitamin D3: 16.73 μg mL−1). The emulsion loaded with nanoparticles minimized the degradation of vitamin D3 when compared with the nanoparticle dispersion. Additionally, the emulsion provided the skin permeation of vitamin D3 following the recommended daily allowance. Conclusion: To the best of our knowledge, this is the first study to use nanostructured lipid carriers for transdermal delivery of vitamin D. The developed formulation is a promising strategy to overcome the vitamin D3 variable oral bioavailability. It also represents a comfortable route of administrationd. Thus it could be beneficial for patients and clinicians. However, further studies are needed to allow the permeation of larger amounts of vitamin D3, and the combination of these nanoparticles with microneedles would be interesting.

scholarly journals Solid nanostructured lipid carriers loaded with silymarin for oral delivery: Formulation development and evaluation

2021 ◽  
Vol 3 (4) ◽  
pp. 56-67
Author(s):  
Rajashree Hirlekar ◽  
Esha Patil ◽  
Srinivas Bhairy
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Drug Loading ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Formulation Development ◽  
Ex Vivo Permeation

The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of silymarin loaded nanostructured lipid carriers (NLCs). The prepared silymarin loaded NLCs and DANs were characterized for various quality parameters. Silymarin loaded NLCs were prepared by a modified hot melt emulsification ultra-sonication method using glyceryl monostearate (GMS), capmul MCM C8 EP (CAP) and gelucire 50/13 (G50/13) as solid lipid, liquid lipid and surfactant respectively. For better stability, NLC dispersion was converted into DANs by adsorbing them onto some suitable carriers. NLCs and DANs were characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, assay, thermal behavior, crystallinity and morphological study. The optimized NLCs have a mean particle size of 206.1±012.5 nm (size distribution of 0.249±0.058), a zeta potential of -32.5±1.2 mV with high entrapment of 95.60±0.45% and drug loading of 1.90±0.08%. The X-ray diffraction and endothermic peaks confirmed the maximum encapsulation of active in lipid matrices. The particles were spherical with smooth surface morphology. In-vitro release studies showed sustained drug release for up to 24 h. Ex-vivo permeation in the presence and absence of lymphatic blocker indicates the uptake of silymarin loaded NLCs by the lymphatic route. Silymarin loaded NLCs prepared had a nanosize distribution with high entrapment efficiency. The ex-vivo permeation study for optimized NLC formulation exhibited the lymphatic uptake of active. Dispersion stability was increased by preparing the DANs. The solid dry powder is used for oral reconstitution and can be further converted into tablets or filled into capsules.

scholarly journals Ex-vivo Ex-Vivo Absorption Study of a Novel Dabigatran Etexilate Loaded Nanostructured Lipid Carrier Using Non-Everted Intestinal Sac Model

2019 ◽  
Vol 28 (2) ◽  
pp. 37-45
Author(s):  
Haithem N Abed ◽  
Ahmed A. Hussein
Keyword(s):  
Particle Size ◽  
Oleic Acid ◽  
Zeta Potential ◽  
Oral Absorption ◽  
Ex Vivo ◽  
Dabigatran Etexilate ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carrier ◽  
Loading Capacity ◽  
Intestinal Permeation

Abstract The purpose of our study was to develop Dabigatran Etexilate loaded nanostructured lipid carriers (DE-NLCs) using Glyceryl monostearate and Oleic acid as lipid matrix, and to estimate the potential of the developed delivery system to improve oral absorption of low bioavailability drug, different Oleic acid ratios effect on particle size, zeta potential, entrapment efficiency and loading capacity were studied, the optimized DE-NLCs shows a particle size within the nanorange, the zeta potential (ZP) was 33.81±0.73mV with drug entrapment efficiency (EE%) of  92.42±2.31% and a loading capacity (DL%) of 7.69±0.17%. about 92% of drug was released in 24hr in a controlled manner, the ex-vivo intestinal permeation study using the non-everted sac model shows four folds increment in the permeation of DE-NLCs compared to dabigatran etexilate suspension (DE-S).

scholarly journals Topical Delivery of Meloxicam using Liposome and Microemulsion Formulation Approaches

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 282 ◽  
Author(s):  
Julia Zhang ◽  
Anna Froelich ◽  
Bozena Michniak-Kohn
Keyword(s):  
Transdermal Delivery ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Entrapment Efficiency ◽  
Topical Delivery ◽  
Onset Of Action ◽  
Promising Alternative ◽  
Inflammatory Drugs ◽  
Systemic Onset

The aim of this study is to develop, characterize and compare conventional liposome, deformable liposome (transfersome) and microemulsion formulations as potential topical delivery systems for meloxicam. Liposomes were characterized in terms of vesicle size, zeta potential and entrapment efficiency. For microemulsions, particle size, electrical conductivity and viscosity studies were performed to assess the structure of the investigated systems. An ex vivo skin permeation study has been conducted to compare these formulations. The dermal and transdermal delivery of meloxicam using these formulations can be a promising alternative to conventional oral delivery of non-steroidal anti-inflammatory drugs (NSAIDs) with enhanced local and systemic onset of action and reduced side effects.

scholarly journals Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 197 ◽  
Author(s):  
Doaa Hassan ◽  
Rehab Abdelmonem ◽  
Menna Abdellatif
Keyword(s):  
Particle Size ◽  
Intraocular Pressure ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Duration Of Action ◽  
Corneal Permeability ◽  
Glaucoma Treatment

This study evaluated the efficacy of cationic nanoparticle (leciplex) to deliver carvedilol to ocular surface for glaucoma treatment as recent studies pointed out the effect of topical carvedilol on intraocular pressure, therefore carvedilol loaded leciplex formulae were prepared using soy phosphatidyl choline (SPC) and cationic surfactant (CTAB/DDAB) and characterized for morphology, entrapment efficiency, particle size, zeta potential and ex-vivo corneal permeation. Then the selected formula was evaluated via in-vivo studies in comparison with carvedilol solution. Leciplex nanoparticles appeared spherical in shape with entrapment efficiency exceeded 95% in all formulae. Leciplex formula composed of SPC and DDAB in (1:1) molar ratio showed the smallest particle size (16.04 ± 1.2 nm), highest zeta potential value (53.9 ± 0.91 mv) and highest apparent corneal permeability coefficient (0.1157 cm/h). Carvedilol leciplex reduced intraocular pressure (IOP) to normal range in ocular hypertensive rabbits after 30 min and duration of action lasted for 24 h, while carvedilol solution reduced IOP to normal value after 60 min and duration of action lasted for 6 h. Furthermore, histological examination of eyeballs of rabbits treated with carvedilol leciplex showed improvement of retinal atrophy of glaucomatous eyes. This study concluded that leciplex improve transcorneal permeation and bioavailability of carvedilol.

scholarly journals Two-Step Optimization to Develop a Transdermal Film Loaded With Dapoxetine Nanoparticles: A Promising Technique to Improve Drug Skin Permeation

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092385
Author(s):  
Tarek A. Ahmed ◽  
Asmaa M. S. Alay ◽  
Solomon Z. Okbazghi ◽  
Nabil A. Alhakamy
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Mode Of Delivery ◽  
Entrapment Efficiency ◽  
Factors Affecting ◽  
Ex Vivo Permeation ◽  
Ex Vivo Permeation Study ◽  
Transdermal Film ◽  
New Formulation

Dapoxetine (DPX) is an orally administered drug for the treatment of premature ejaculation (PE). One of the challenges of administering DPX orally as a tablet is its poor bioavailability (ie, 42%) due to extensive first-pass metabolism. Thus, it is vital to develop a new formulation and mode of delivery to achieve the unmet needs of PE treatment. In this study, an optimized DPX polymeric nanoparticle (PNP) was developed and subsequently loaded into a transdermal film. The Box–Behnken design was utilized to optimize 3 formulation factors affecting the particle size and entrapment efficiency (EE) of chitosan (CS)-alginate (ALG) PNPs. A 3-level factorial design was used to study the effect of 2 variables affecting DPX cumulative percent released and percent elongation from transdermal films loaded with DPX-PNPs. Permeation parameters were calculated following ex vivo permeation study through rat skin. Transport of the PNPs across the skin layers was investigated using a fluorescence laser microscope. Results revealed that an optimized PNPs formulation was developed with a particle size 415.94 nm and EE 37.31%. Dapoxetine was successfully entrapped in the polymeric matrix. Chitosan and ALG interacted electrostatically with the studied cross-linking agents to form a polyelectrolyte complex. The ex vivo study illustrated a sustained release profile of DPX with enhanced skin permeation from the film loaded PNPs. Moreover, the PNPs was able to penetrate deeper into skin layers. Therefore, DPX transdermal film developed in this work could be considered as a successful drug delivery with better patient compliance for the treatment of PE.

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

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.

scholarly journals Formulation and Evaluation of Clarithromycin Loaded Nanostructured Lipid Carriers for the Treatment of Acne

2021 ◽  
pp. 26-38
Author(s):  
Pooja Shettigar ◽  
Marina Koland ◽  
S. M. Sindhoor ◽  
Ananth Prabhu
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Drug Release ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
In Vitro Drug Release ◽  
Ex Vivo Permeation ◽  
Acne Treatment

Background: Clarithromycin is a macrolide antibiotic used in acne treatment, but it has poor solubility, which decreases its permeability through lipid barriers such as skin. Nanostructured lipid carriers can enhance the permeability of clarithromycin through the skin, thus improving its potential for controlling acne. Aim: To formulate and evaluate Nanostructured lipid carriers of clarithromycin for topical delivery in acne treatment Methods: Nanostructured lipid carriers were prepared by emulsification and ultrasonication methods using lipids such as glycerol monostearate and oleic with poloxamer 188 as stabilizer. These nano-carriers were optimized with the help of the Quality by Design (QbD) approach employing Design-Expert® software. The nanoparticles were characterized for particle size analysis, zeta potential, drug-excipient compatibility, entrapment efficiency, and surface morphology by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The nano-carriers were also investigated for in vitro drug release and ex vivo permeation through excised goat skin. The optimized formulation was incorporated into topical carbopol gel base, formulated and examined for pH, viscosity, spreadability, in vitro drug release, ex vivo permeation, and stability under accelerated conditions. Results: The average particle size of the optimized nanoparticles was 164.8 nm, and zeta potential was -39.2 mV. FTIR studies showed that drug and lipids are compatible with each other. The morphology study by SEM and TEM showed spherical shaped particles. The entrapment efficiency of the optimized formulation was found to be 88.16%. In vitro drug release studies indicated sustained release from the formulation due to diffusion through the lipid matrix of the particles. The ex vivo permeation study using goat skin produced greater permeation from the NLC gel (89.5%) than marketed gel (65%) due to the lipid solubility of the nanoparticles in the skin. The formulation was stable under accelerated conditions. Conclusion: The optimized formulation can be considered as promising nano-carriers suitable for the sustained release of clarithromycin into the skin for effective control of acne.

scholarly journals Development and Evaluations of Transdermally Delivered Luteolin Loaded Cationic Nanoemulsion: In Vitro and Ex Vivo Evaluations

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1218
Author(s):  
Mohammad A. Altamimi ◽  
Afzal Hussain ◽  
Sultan Alshehri ◽  
Syed Sarim Imam ◽  
Usamah Abdulrahman Alnemer
Keyword(s):  
Drug Release ◽  
Zeta Potential ◽  
Transdermal Delivery ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Oral Drug ◽  
In Vitro Drug Release ◽  
Drug Deposition ◽  
Drug Content

Introduction: Luteolin (LUT) is natural flavonoid with multiple therapeutic potentials and is explored for transdermal delivery using a nanocarrier system. LUT loaded cationic nanoemulsions (CNE1–CNE9) using bergamot oil (BO) were developed, optimized, and characterized in terms of in vitro and ex vivo parameters for improved permeation. Materials and methods: The solubility study of LUT was carried out in selected excipients, namely BO, cremophor EL (CEL as surfactant), labrasol (LAB), and oleylamine (OA as cationic charge inducer). Formulations were characterized with globular size, polydispersity index (PDI), zeta potential, pH, and thermodynamic stability studies. The optimized formulation (CNE4) was selected for comparative investigations (% transmittance as %T, morphology, chemical compatibility, drug content, in vitro % drug release, ex vivo skin permeation, and drug deposition, DD) against ANE4 (anionic nanoemulsion for comparison) and drug suspension (DS). Results: Formulations such as CNE1–CNE9 and ANE4 (except CNE6 and CNE8) were found to be stable. The optimized CNE4 based on the lowest value of globular size (112 nm), minimum PDI (0.15), and optimum zeta potential (+26 mV) was selected for comparative assessment against ANE4 and DS. The %T values of CNE1–CNE9 were found to be ˃95% and CEL content slightly improved the %T value. The spherical CNE4 was compatible with excipients and showed % total drug content in the range of 97.9–99.7%. In vitro drug release values from CNE4 and ANE4 were significantly higher than DS. Moreover, permeation flux (138.82 ± 8.4 µg/cm2·h), enhancement ratio (8.23), and DD (10.98%) were remarkably higher than DS. Thus, ex vivo parameters were relatively high as compared to DS which may be attributed to nanonization, surfactant-mediated reversible changes in skin lipid matrix, and electrostatic interaction of nanoglobules with the cellular surface. Conclusion: Transdermal delivery of LUT can be a suitable alternative to oral drug delivery for augmented skin permeation and drug deposition.

Development and optimization of Luliconazole Nanostructured lipid carriers based gel by Quality by Design its skin distribution studies, dermatokinetic modeling & In-vitro and Ex-vivo correlation

2020 ◽  
Vol 18 ◽  
Author(s):  
Eranti Bhargav ◽  
Yiragamreddy Padmanabha Reddy ◽  
Koteshwara Kunnatur B
Keyword(s):  
Particle Size ◽  
Quality By Design ◽  
Fungal Infections ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Fractional Factorial ◽  
Sonication Time ◽  
Drug Concentrations

Objective : The present study was aimed to improve the permeability of Luliconazole (LZ) and to localize high drug concentrations at skin layers by Quality by Design (QbD) based Nanostructured lipid carriers (NC) based gel. Methods: Quality Target Product Profile was set and Critical Quality attributes were identified. FT-IR and DSC studies confirmed compatibility. Risk assessment was carried out by screening the factors using 27-27-2 fractional factorial design and optimization by Box Behnken design. Cholesterol: Cetyl Palmitate, PEG 200 and probe sonication time were identified as factors, Particle size (<200 nm), PDI (0.4), % Entrapment efficiency (% EE, >80%) and % Cumulative Drug release (% CDR, >95%) as responses. Contour plots, Overlay plots and desirability were utilized to create design space. Results: The quadratic polynomial equations showed that increased lipid content, PEG 200 and optimum sonication time reduced Particle size, PDI, improved % EE and % CDR. The optimized formula was formulated into a gel. Ex-vivo permeation studies performed using pig ear pinna skin revealed that developed LZ NC gel exhibited greater permeation 272.98±8.57 (µg/cm2 ) and 32.11 ±4.7 (µg/cm2 /h) flux than plain drug dispersed gel. Dermatokinetic parameters of LZ NC gel revealed that highly significant amount of LZ was permeated, distributed and transported through the skin layers. The better linear correlations were obtained by LZ permeation through synthetic membrane (in-vitro) and pig ear pinna skin (ex-vivo). Conclusion: The above findings revealed that developed LZ NC gel exhibited better permeation and localization at skin layers in treating fungal infections.

scholarly journals DEVELOPMENT AND CHARACTERIZATION OF PIPER RETROFRACTUM EXTRACT LOADED MUCOADHESIVE NANOSTRUCTURED LIPID CARRIERS FOR TOPICAL ORAL DRUG DELIVERY

2017 ◽  
Vol 9 (9) ◽  
pp. 79
Author(s):  
Kavee Srichaivatana ◽  
Anan Ounaroon ◽  
Waree Tiyaboonchai
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Zeta Potential ◽  
Oral Cavity ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Oral Drug ◽  
Drug Entrapment Efficiency ◽  
Piper Retrofractum

Objective: To develop and characterize Piper retrofractum extract loaded nanostructured lipid carriers (PRE loaded NLCs) for topical oral cavity administration to enhance bioavailability and stability of piperine.Methods: PRE loaded NLCs were prepared with a hot high-pressure homogenization technique followed by coating the particle surface with mucoadhesive polymers; polyethene glycol 400 (PEG) and polyvinyl alcohol (PVA). The physicochemical properties in terms of particle size, polydispersity index, zeta potential, drug entrapment efficiency, in vitro drug release profile and antimicrobial activities were examined. In vitro, mucoadhesion studies were assessed by the wash-off test. The physicochemical stabilities of mouth spray containing PRE loaded NLCs were investigated by kept at room temperature and 4 °C for 6 mo.Results: The PRE loaded NLCs showed spherical shape with a mean particle size of ~100-120 nm and zeta potential of ~-24 mV. Up to 90% drug entrapment efficiency was achieved. PEG-NLCs and PVA-NLCs showed a strong interaction with porcine buccal mucosa than uncoated-NLCs. All PRE loaded NLCs formulations revealed fast release characteristics and effective against Streptococcus mutans and S. sanguinis. The mouth spray containing PRE loaded NLCs showed good physical stability without particle aggregation. In addition, the chemical stability of piperine in NLCs was significantly improved during storage at both storage conditions compared to its solution form.Conclusion: The developed PRE loaded polymer coated-NLCs showed high potential to use as a local drug delivery system for reducing the bacterial growth in the oral cavity.

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