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

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).

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

Pharmaceutics ◽

10.3390/pharmaceutics10040197 ◽

2018 ◽

Vol 10 (4) ◽

pp. 197 ◽

Cited By ~ 9

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.

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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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An Innovative Formulation Based on Nanostructured Lipid Carriers for Imatinib Delivery: Pre-Formulation, Cellular Uptake and Cytotoxicity Studies

Nanomaterials ◽

10.3390/nano12020250 ◽

2022 ◽

Vol 12 (2) ◽

pp. 250

Author(s):

Evren Gundogdu ◽

Emine-Selin Demir ◽

Meliha Ekinci ◽

Emre Ozgenc ◽

Derya Ilem-Ozdemir ◽

...

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Cellular Uptake ◽

Enzyme Inhibitor ◽

Release Kinetics ◽

In Vitro Release ◽

Nanostructured Lipid Carrier ◽

Loading Capacity ◽

Cytotoxicity Studies

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification–sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and −32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer–Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

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Formulation and In Vitro Evaluation of Casein Nanoparticles as Carrier for Celecoxib

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2020.049 ◽

2020 ◽

Vol 10 (3) ◽

pp. 408-417

Author(s):

Jyotsana R. Madan ◽

Izharahemad N. Ansari ◽

Kamal Dua ◽

Rajendra Awasthi

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Ex Vivo ◽

Entrapment Efficiency ◽

Water Soluble ◽

Polydispersity Index ◽

Drug Dissolution ◽

Permeation Studies ◽

Poorly Water Soluble

Purpose : The objective of this work was to formulate casein (CAS) nanocarriers for the dissolution enhancement of poorly water soluble drug celecoxib (CLXB). Methods: The CLXB loaded CAS nanocarriers viz., nanoparticles, reassembled CAS micelles and nanocapsules were prepared using sodium caseinate (SOD-CAS) as a carrier to enhance the solubility of CLXB. The prepared formulations were characterized for particle size, polydispersity index, zeta potential, percentage entrapment efficiency, and surface morphology for the selection of best formulation. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction study was used to for the confirmation of encapsulation of CLXB. Further, in vitro drug dissolution, ex-vivo permeation studies on chicken ileum and stability studies were carried out. Results: The CLXB loaded casein nanoparticles (CNP) (batch A2) showed a particle size diameter 216.1 nm, polydispersity index 0.422 with percentage entrapment efficiency of 90.71% and zeta potential of -24.6 mV. Scanning electron microscopy of suspension confirmed globular shape of CNP. The in vitro release data of optimized batch followed non Fickian diffusion mechanism. The ex vivo permeation studies on chicken ileum of CLXB loaded CNP showed permeation through mucous membrane as compared to pure CLXB. The apparent permeability of best selected freeze dried CLXB loaded CNP (batch A2) was higher and gradually increased from 0.90 mg/cm2 after 10 min to a maximum of 1.95 mg/cm2 over the subsequent 90 min. A higher permeation was recorded at each time point than that of the pure CLXB. Conclusion: The study explored the potential of CAS as a carrier for solubility enhancement of poorly water soluble drugs.

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Formulation and Evaluation of Polymeric Nanomicelles of Gliptin for Controlled Drug Delivery

Drug Delivery Letters ◽

10.2174/2210303109666190212112505 ◽

2019 ◽

Vol 9 (2) ◽

pp. 146-156 ◽

Cited By ~ 1

Author(s):

Deepika Sharma ◽

Bhavna Kumar

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Drug Release ◽

Zeta Potential ◽

Polymer Concentration ◽

Controlled Drug Delivery ◽

Entrapment Efficiency ◽

Loading Capacity ◽

Dissolution Method ◽

Direct Dissolution

Objective: The main objective of the study was to develop gliptin loaded polymeric nanomicelles by direct dissolution method. The comparative evaluation studies were performed to study the effect of polymer concentration on particle size, entrapment efficiency, loading capacity and drug release of the formulation. Methods: Gliptin loaded polymeric nanomicelles were prepared by the direct dissolution method. The formulations were prepared by varying the concentration of polymer and drug concentration was kept constant in all the formulations. The concentration of polymer (pullulan) was maintained 0.1%, 0.5% 1% in formulation F-1, F-2 and F-3, respectively. The effect of polymer concentration on mean particle size, zeta potential, % entrapment efficiency, % loading capacity and in vitro drug release was studied. Results: The optimized nanoformulation was obtained with pullulan 0.1% concentration with a mean particle diameter of 368.2nm and zeta potential value (-7.96mV) indicating greater stability. Conclusion: Hence F-1 was considered to be the best formulation for the preparation of gliptin loaded polymeric nanomicelles. Hence, it can be concluded that polymeric nanomicellar approach can be beneficial to improve the bioavailability and poor permeability of class III drugs like gliptins and thus can be a better approach for controlled drug delivery.

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Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet

Molecules ◽

10.3390/molecules26051485 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1485

Author(s):

Yogeeta O. Agrawal ◽

Umesh B. Mahajan ◽

Vinit V. Agnihotri ◽

Mayur S. Nilange ◽

Hitendra S. Mahajan ◽

...

Keyword(s):

Particle Size ◽

Zeta Potential ◽

High Fat Diet ◽

Entrapment Efficiency ◽

Polydispersity Index ◽

Nanostructured Lipid Carrier ◽

High Fat ◽

Scanning Calorimetry ◽

Bioavailability Enhancement

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of −28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.

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A Perspective View on Formulation and Optimization of Curcumin Loaded Phycocyanin Nanosponges

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.4874 ◽

2020 ◽

Vol 11 (4) ◽

pp. 8119-8123

Author(s):

Manjuladevi Kasirajan ◽

Ramaiyan Velmurugan

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Positive Impact ◽

Entrapment Efficiency ◽

Phase Ratio ◽

Loading Capacity ◽

Perspective View ◽

Wide Range ◽

Different Response ◽

O Phase

Curcumin have a wide range of pharmacological activity and used in various disorders. Due to its poor bioavailability and fast metabolism peripherally, it is a major obstacle for researchers. Recent research on nanotechnology paved the way to overcome above concern and good results were obtained in formulation of curcumin using nanotechnology. The main objective of the study is to optimize, formulate & develop the curcumin loaded phycocyanin nanosponges and determine the variation in responses with respect to factors. The nanosponges were prepared using solvent evaporation technique and the final curcumin loaded Phycocyanin nanosponges (Cur-PC-NS) formulation is optimized and characterized. The formulation factors like drug polymer ratio, Aqueous/ Organic (A/O) phase ratio, concentrations of surfactant, Sonication & stirring time were considered as function excipient have shown different response values in aspects of Particle Size (PS), Zeta Potential (ZP), % of entrapment efficiency (EE%) & Loading capacity (LC%). In our findings F8 formulated nanosponges got 121.9nm particle size; -25.1mV zeta potential; 84.98% of Entrapment efficiency & 52.92% of loading capacity. Thus exhibited change in A/O phase ratio, surfactant concentration & Sonication time are 5:1, 0.5%, 1 hour respectively which have great impact on PS, EE% & LC%. We conclude that factor and its positive impact on response have to be taken in concern and utilized; we can develop better sustain release curcumin loaded phycocyanin nanosponges

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

Current Drug Delivery ◽

10.2174/1567201818666210708121304 ◽

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.

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Design, Formulation, In-Vitro and Ex-Vivo Evaluation of Atazanavir Loaded Cubosomal Gel

Biointerface Research in Applied Chemistry ◽

10.33263/briac114.1203712054 ◽

2020 ◽

Vol 11 (4) ◽

pp. 12037-12054

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Ex Vivo ◽

Entrapment Efficiency ◽

Relative Bioavailability ◽

Transdermal Application ◽

Study Results ◽

Nano Formulation

In this study, Atazanavir (ATZ) was designed into the Nano formulation called cubosomes to improve its bioavailability and curtail the adverse effects by the transdermal route delivery of ATZ -loaded cubosomes. Around twenty cubosomal formulations were formulated using a Central composite factorial design. The effect of glyceryl monooleate (GMO), surfactant (Pluronic F 127), and Cetyltrimethylammonium bromide (CTAB) were studied using processes of emulsification and homogenization. Different concentrations of independent variables on particle size distribution, zeta potential, and entrapment efficiency were determined. FTIR, DSC, X-ray, and SEM, TEM results established that the drug was encapsulated in the cubosomes. The results suggested that the optimal formula exhibited a particle size of 100±7.9 - 345±6.4 nm and entrapment efficiency ranging from 61±4.6 - 93±0.8, zeta potential values ranging from -24.51 to -32.45 mV, polydispersity index values ranged from 0.35±0.01-0.54±0.02 of ATZ. The in vitro studies showed a controlled release pattern of drug release up to 24h. The ATZ cubosomal gel application on the in vivo absorption studies of the drug was studied in rats and compared with oral ATZ solution. The in vivo study results showed that the transdermal application of ATZ cubosomal gel considerably improves the absorption of drug compared to that of oral ATZ solution and found that the relative bioavailability is 4.6 times greater of oral ATZ solution. Thus it can be concluded that the ATZ cubosomal gel application via transdermal delivery route has the potential in increasing the bioavailability of the drug.

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

Current Trends in Pharmacy and Pharmaceutical Chemistry ◽

10.18231/j.ctppc.2021.014 ◽

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.

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