Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery

2020 ◽  
Vol 13 (6) ◽  
pp. 5250-5255
Author(s):  
Ashwin Kumar Tulasi ◽  
Anil Goud Kandhula ◽  
Ravi Krishna Velupula
Keyword(s):  
Particle Size ◽  
Nasal Mucosa ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Chemical Properties ◽  
Brain Targeting ◽  
Oral Tablet ◽  
Promising Alternative ◽  
Ex Vivo Permeation

Topiramate is a second-generation antiepileptic drug used in partial, generalized seizures as an oral tablet. Oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Hence, the present study was aimed to develop topiramate mucoadhesive nanoparticles for intranasal administration using ionotropic gelation method. The developed nanoparticles were evaluated for physico-chemical properties like particle size, zeta potential, surface morphology, drug content, entrapment efficiency, in vitro drug release, mucoadhesive strength, and ex vivo permeation studies in excised porcine nasal mucosa. Optimized nanoparticle formulation (T9) was composed oil mucoadhesive agent (Chitosan 1% w/w), cross linking polymer (TPP) and topiramate 275mg, 100mg and 4% respectively. It showed particle size of 350nm, high encapsulation efficacy and strong mucoadhesive strength. In vitro drug diffusion of optimized formulation showed 95.12% release of drug after 180min. Ex-vivo permeation of drug across nasal mucosa was   88.05 % after 180min. Nasocilial toxicity studies showed optimized formulation did not damage the nasal mucosa. Thus, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

scholarly journals INTRANASAL TOPIRAMATE POLYMERIC NANOPARTICLES FOR EPILEPSY: IN VITRO AND EX-VIVO INVESTIGATION

2020 ◽  
pp. 258-264
Author(s):  
PRAVIN KUKUDKAR ◽  
SONIYA RAHATE ◽  
RASHMI TRIVEDI ◽  
MILIND UMEKAR ◽  
JAYSHREE TAKSANDE
Keyword(s):  
Nasal Mucosa ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Crosslinking Agent ◽  
Brain Targeting ◽  
Promising Alternative ◽  
Drug Diffusion ◽  
Treatment Of Epilepsy ◽  
Ex Vivo Permeation

Objective: The presence of tight junctions in blood-brain barrier creates a major problem for the delivery of drugs and severely affects adequate therapeutic concentration to reach the brain. For the treatment of epilepsy, oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Thus, an alternative route of drug delivery is highly desirable for an effective outcome. Methods: In the present study, bioadhesive chitosan nanoparticles of topiramate for intranasal administration were prepared by ionotropic gelation method using chitosan as bioadhesive polymer and sodium tripolyphosphate as the crosslinking agent. The prepared nanoparticles were evaluated for physicochemical properties like particle size, surface morphology, drug content, entrapment efficiency, thermal behavior and crystallinity, in vitro drug diffusion, ex vivo bio adhesion, and ex vivo biocompatibility studies in excised sheep nasal mucosa. Results: Differential scanning calorimetry and x-ray diffraction study showed molecular dispersion of drug into the polymer matrices and conversion of it into an amorphous form. Nanoparticles obtained were discrete in nature (size 313.5 nm) and appropriate for intranasal administration. The topiramate nanoparticles revealed high encapsulation efficacy, strong bioadhesion potential and high ex vivo permeation and did not exhibit any deformity to the nasal mucosa. In vitro drug diffusion of optimized formulation showed 92.91% release of drugs after 180 min. Ex-vivo permeation of drugs across nasal mucosa was 89.03 % after 180 min. Conclusion: Hence, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

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.

PLGA nanoparticles for nose to brain delivery of Clonazepam: formulation, optimization by 32 Factorial design, in vitro and in vivo evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Pranav Shah ◽  
Jayant Sarolia ◽  
Bhavin Vyas ◽  
Priti Wagh ◽  
Kaul Ankur ◽  
...  
Keyword(s):  
Particle Size ◽  
Factorial Design ◽  
Intranasal Administration ◽  
Plga Nanoparticles ◽  
Brain Targeting ◽  
Rabbit Brain ◽  
Histopathological Study ◽  
In Vivo Evaluation

Background: Intranasal administration of biodegradable nanoparticles has been extensively studied for targeting the drug directly to CNS through olfactory or trigeminal route bypassing blood brain barrier. Objective: The objective of the present study was to optimize Clonazepam loaded PLGA nanoparticles (CLO-PNPs) by investigating the effect of process variables on the responses using 32 full factorial design. Methods: Effect of two independent factors-amount of PLGA and concentration of Poloxamer 188, were studied at low, medium and high levels on three dependent responses-%Entrapment efficiency, Particle size (nm) and %cumulative drug release at 24hr. Results: %EE, Particle size and %CDR at 24hr of optimized batch was 63.7%, 165.1 nm and 86.96% respectively. Nanoparticles were radiolabeled with 99mTc and biodistribution was investigated in BALB/c mice after intranasal & intravenous administrations. Significantly higher brain/blood uptake ratios and AUC values in brain following intranasal administration of CLO-PNPs indicated more effective brain targeting of CLO. Higher brain uptake of intranasal CLO-PNPs was confirmed by rabbit brain scintigraphy imaging. Histopathological study performed on goat nasal mucosa revealed no adverse response of nanoparticles. TEM image exhibited spherical shaped particles in nano range. DSC and XRD studies suggested Clonazepam encapsulation within PLGA matrix. The onset of occurrence of PTZ-induced seizures in rats was significantly delayed by intranasal nanoparticles as compared to intranasal & intravenous CLO-SOL. Conclusion: This investigation exhibits rapid rate and higher extent of CLO transport in brain with intranasal CLO-PNPs suggesting a better option as compared to oral & parenteral route in management of acute status epilepticus.

scholarly journals DoE Directed Optimization, Development and Characterization of Resveratrol Loaded Nlc System for the Nose to Brain Delivery in the Management of Glioblastoma Multiforme

2021 ◽  
Author(s):  
Nitish Kumar ◽  
Ghanshyam Das Gupta ◽  
Daisy Arora
Keyword(s):  
Particle Size ◽  
Nasal Mucosa ◽  
Ex Vivo ◽  
Research Work ◽  
Spherical Shape ◽  
Entrapment Efficiency ◽  
Antioxidant Property ◽  
Brain Delivery ◽  
Antioxidant Assay

Abstract Nose to brain delivery of resveratrol can be a very useful method to overcome the limitations possessed by conventional delivery approaches namely, hepatic metabolism, low bioavailability and half-life of resveratrol, and presence of blood-brain barrier (BBB). The objective of this research work was to develop and optimize the resveratrol-loaded NLCs and coating these carriers with chitosan to increase the residence time of the formulation into the nasal cavity and enhanced permeation across the nasal mucosa. Three CQAs (Particle size, Entrapment efficiency, and PDI), and CMAs (Solid: total lipid concentration, surfactant concentration, and bioactive amount) were selected and the formulation was optimized using the Box-Behnken design (BBD) approach. The optimized batch was evaluated for physicochemical characteristics such as particle size (168.24 ± 8.24 nm), PDI (0.151 ± 0.003), and entrapment efficiency (77.42 ± 3.76 %). This optimized batch was coated with chitosan, which produced coated NLCs with a particle size of 317.7 ± 15.9 nm, and PDI was 0.089 ± 0.009. The morphological study using TEM confirmed the spherical shape, size, and surface coating of the NLCs. Furthermore, both the uncoated and coated particles were analyzed for in vitro resveratrol release, ex vivo diffusion study, and antioxidant assay. NLCs was founded to show sustained in vitro release characteristic, and enhanced bioactive diffusion across the nasal mucosa compared to the bioactive solution of resveratrol. The antioxidant assay revealed that the antioxidant property of resveratrol was intact in the formulation, and a slight increase in antioxidant activity of the formulation was also observed which may be due to the presence of sesame oil in the formulation. These results indicated that the chitosan-coated NLCs can be used to deliver therapeutic moieties more efficiently via the nose to brain drug delivery.

scholarly journals Development and In Vitro/In Vivo Evaluation of pH-Sensitive Polymeric Nanoparticles Loaded Hydrogel for the Management of Psoriasis

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3433
Author(s):  
Muhammad Imran Asad ◽  
Dildar Khan ◽  
Asim ur Rehman ◽  
Abdelhamid Elaissari ◽  
Naveed Ahmed
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Ex Vivo ◽  
Skin Irritation ◽  
Topical Formulation ◽  
Sustained Drug Release ◽  
In Vivo Evaluation ◽  
Ex Vivo Permeation ◽  
Pasi Score

Methotrexate (MTX), the gold standard against psoriasis, poses severe problems when administered systemically viz increased toxicity, poor solubility and adverse reactions. Hence, a topical formulation of MTX for the management of psoriasis can be an effective approach. The present study aimed to develop an MTX based nanoparticle-loaded chitosan hydrogel for evaluating its potential efficacy in an imiquimod-induced psoriatic mice model. MTX-NPs loaded hydrogel was prepared and optimized using the o/w emulsion solvent evaporation method. Particle size, zeta potential, entrapment efficiency, in vitro drug release, ex vivo permeation, skin irritation and deposition studies were performed. Psoriatic Area and Severity Index (PASI) score/histopathological examinations were conducted to check the antipsoriatic potential of MTX-NPs loaded hydrogel using an imiquimod (IMQ)-induced psoriatic model. Optimized MTX-NPs showed a particle size of 256.4 ± 2.17 nm and encapsulation efficiency of 86 ± 0.03%. MTX-NPs loaded hydrogel displayed a 73 ± 1.21% sustained drug release in 48 h. Ex vivo permeation study showed only 19.95 ± 1.04 µg/cm2 of drug permeated though skin in 24 h, while epidermis retained 81.33% of the drug. A significant decrease in PASI score with improvement to normalcy of mice skin was observed. The developed MTX-NPs hydrogel displayed negligible signs of mild hyperkeratosis and parakeratosis, while histopathological studies showed healing signs of mice skin. So, the MTX-NPs loaded hydrogel can be a promising delivery system against psoriasis.

scholarly journals Design and Evaluation of Natamycin Nanocrystals Loaded In Situ Gel for Ophthalmic Administration

2021 ◽  
pp. 307-324
Author(s):  
Roshni Das ◽  
Marina Koland ◽  
S. M. Sindhoor
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Ex Vivo ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
Drug Content ◽  
Ex Vivo Permeation

Background: Natamycin belongs to a large group of naturally occurring polyene antifungal antibiotics derived from Streptomyces natalensis. Natamycin has a restrictive pharmaceutical role because of its extremely low aqueous solubility, which severely reduces the bioavailability of the drug. To improve the absorption of the drug, nanocrystals of natamycin were prepared and incorporated into in situ gel. Aim: To improve the solubility and absorption of natamycin nanocrystals by preparing nanocrystal in situ gel of natamycin for ophthalmic delivery Methodology: Natamycin nanocrystal was prepared using Sono-Precipitation method. Box-Behnken approach was employed to assess the influence of independent variables, namely concentration of stabilizer, sonication time and amplitude on particle size and zeta potential of the prepared nanocrystal. Optimized natamycin nanocrystal in situ gel formulations was characterized for various parameters like pH, viscosity, drug content, in vitro drug release and ex vivo permeation studies. Results: The optimized formulation of natamycin nanocrystal with a particle size of  293.9nm and zeta potential -14.6mV was incorporated into in situ gels. The pH triggered in situ gel was prepared using Carbopol and Hydroxypropyl methylcellulose (HPMC)., which showed clear preparation, pH of the formulation was closed to the pH of tear fluid, i.e., 7.4, viscosity showed pseudoplastic behaviour with immediate gelation remained for an extended period, and the drug content was around 99.70%. From the characterizations given above, PF-4 was optimized and evaluated for In vitro drug release showing slow and sustained release when compared to the marketed formulation and followed first-order kinetics with the diffusion-controlled mechanism. Ex vivo permeation through goat's cornea of PF-4 showed better permeation than marketed formulation. The stability studies of PF-4 showed that formulation was stable at the appropriate condition. Conclusion: Nanocrystals formulations of natamycin was successfully formulated and incorporated into in situ gels. Further in vivo studies need to be carried out for confirmation of pharmacological activity

Design and Optimization of Itraconazole Loaded SLN for Intranasal Administration Using Central Composite Design

2020 ◽  
Vol 10 (6) ◽  
pp. 884-891
Author(s):  
Sarvjeet S. Rana ◽  
Shailendra Bhatt ◽  
Manish Kumar ◽  
Anuj Malik ◽  
Jai B. Sharma ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Ex Vivo Study ◽  
Central Composite

Introduction: Solid Lipid nanoparticles (SLN) are comprising of a solid lipid core with a mean diameter between 50 and 1000 nm. SLN is an advanced carrier system to traditional colloidal carriers such as emulsion, liposomes, and polymeric microparticles. Objective: The objective of this study was to formulate SLN of Itraconazole (ITZ) for intranasal administration. Methods: ITZ-loaded SLN were prepared by high pressure homogenization technique using the Central Composite Design (CCD). The concentration of surfactant (X1) and drug to lipid ratio (X2) was considered as independent variables, whereas particle size (Y1) and percentage entrapment efficiency (Y2) were considered as a response. The compatibility of ingredients with the drug was tested using differential scanning calorimetry. SLN were characterized for their particle size, entrapment efficiency, transmission electron microscopy, in vitro drug release, and ex vivo study. Results: The solid lipid nanoparticles were successfully prepared using high pressure homogenization technique and glyceryl monostearate was used as solid lipid. The lipid ratio significantly increases the particle size as well as entrapment efficiency. The particle size and (%) entrapment efficiency of optimized formulation were found to be 29 nm and 78.9%, respectively. The differential scanning calorimetry confirmed that the drug existed in amorphous form. Nasal histopathology study on sheep mucosa revealed that the developed SLN was non-toxic and safe to use for intranasal administration. The results of ex vivo study showed that the Higuchi pattern of drug release was followed. The in vitro release studies showed the significant difference in drug release from ITZ-loaded SLN compared to plain ITZ-solution. Conclusion: ITZ-loaded SLN were successfully prepared and validated. The best batch was selected based on the desired particle size, and EE which is an important characteristic for SLN formulations. The developed formulations were nontoxic as determined by histo-pathological studies.

Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution

2015 ◽  
Vol 490 (1-2) ◽  
pp. 281-291 ◽  
Author(s):  
Fatma Elzahraa Abdelrahman ◽  
Ibrahim Elsayed ◽  
Mary Kamal Gad ◽  
Ahmed Badr ◽  
Magdi Ibrahim Mohamed
Keyword(s):  
Ex Vivo ◽  
Brain Targeting ◽  
In Vivo Biodistribution ◽  
Ex Vivo Permeation

scholarly journals Comparison Between Conventional and Supersaturable Self-nanoemulsion Loaded with Nebivolol: Preparation and In-vitro/Ex-vivo Evaluation

2020 ◽  
Vol 29 (1) ◽  
pp. 216-225
Author(s):  
Lubna A. Sabri ◽  
Ahmed A. Hussein
Keyword(s):  
High Selectivity ◽  
Ex Vivo ◽  
Permeation Rate ◽  
Promising Alternative ◽  
Precipitation Inhibition ◽  
Ex Vivo Permeation ◽  
Alternative Approach ◽  
Polymer Type

Nebivolol (NBH) is a third-generation B1-blocker with high selectivity and vasodilation activity. Nevertheless, nebivolol exhibits low oral bioavailability, which may adversely affect its efficacy. Recently, supersaturable self-nanoemulsion (Su-SNE) is an advanced SNE approach that can address low bioavailability The study aims to prepare nebivolol-loaded Su-SNE by reduction the amount of the prepared conventional SNE to half. Besides, an appropriate polymer type and concentration to prevent NBH precipitation upon oral administration have investigated.. A conventional self-nanoemulsion (formula A) was prepared by dissolving NBH in 500 mg vehicle mixture of imwitor®988: cremophor-EL: propylene glycol. Then, eight Su-SNE formulas with the absence or presence of four different polymers were prepared and evaluated. In-vitro precipitation assay was performed to assess the precipitation inhibition capacity of polymers. The ex-vivo permeation through rat intestinal mucosa was also conducted for determination of permeability parameters. Results revealed that (Su-SNA formula SAS1) containing 5% soluplus could effectively retard the nebivolol precipitation. There was no statistical difference between formula A and SAS1; both maintained a higher apparent NBH concentra­tion for approximately 240 min in 0.1N HCl. The permeation rate of conventional (formula A) and soluplus-based Su-SNE (formula SAS1) was significantly improved, and the permeation enhancement ratio was found 2.7 and 3.2, respectively, as compared with non-formulated NBH. Consequently, it is concluded that developing soluplus-based nebivolol SNE is a promising alternative approach. It can enhance nebivolol stability and permeability with half the amount of conventional SNE components.

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