Design and Evaluation of Long Acting Biodegradable PLGA Microspheres for Ocular Drug Delivery

2019 ◽  
Vol 10 ◽  
Author(s):  
Anjali Pandya ◽  
Rajani Athawale ◽  
Durga Puro ◽  
Geeta Bhagwat
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Degradation Products ◽  
Ex Vivo ◽  
Research Work ◽  
Entrapment Efficiency ◽  
Rational Approach ◽  
Plga Microspheres ◽  
Long Acting

Background: The research work involves development of PLGA biodegradable microspheres loaded with dexamethasome for intraocular delivery. Objective: To design and evaluate long acting PLGA microspheres for ocular delivery of dexamethasone. Method: Present formulation involves the development of long acting dexamethasone loaded microspheres composed of a biodegradable controlled release polymer, Poly(D, L- lactide-co-glycolide) (PLGA), for the treatment of posterior segment eye disorders intravitreally. PLGA with monomer ratio of 50:50 of lactic acid to glycolic acid was used to achieve a drug release up to 45 days. Quality by Design approach was utilized for designing the experiments. Single emulsion solvent evaporation technique along with high pressure homogenization was used to facilitate formation of microspheres. Results: Particle size evaluation, drug content and drug entrapment efficiency were determined for the microspheres. Particle size and morphology was observed using Field Emission Gun-Scanning Electron Microscopy (FEG-SEM) and microspheres were in the size range of 1-5 μm. Assessment of drug release was done using in vitro studies and transretinal permeation was observed by ex vivo studies using goat retinal tissues. Conclusion: Considering the dire need for prolonged therapeutic effect in diseases of the posterior eye, an intravitreal long acting formulation was designed. Use of biodegradable polymer with biocompatible degradation products was a rational approach to achieve this aim. Outcome from present research shows that developed microspheres would provide a long acting drug profile and reduce the frequency of administration thereby improving patient compliance.

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.

Design and Development of Lomustine Loaded Chitosan Nanoparticles for Efficient Brain Targeting

2020 ◽  
Vol 18 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Anupriya Anand ◽  
Bharadhwaj Ramesh Iyer ◽  
Chandrasekar Ponnusamy ◽  
Rajesh Pandiyan ◽  
Abimanyu Sugumaran
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Research Work ◽  
Chitosan Nanoparticles ◽  
Entrapment Efficiency ◽  
Brain Targeting ◽  
P Value ◽  
Drug Content ◽  
Diffusion Controlled

Aim: The present research work discussed the preparation of lomustine loaded with chitosan nanoparticles (LNCp) by ionic gelation method with homogenization using the design on experiments by Box-Behnken design. Methods: The nanoparticles are evaluated by particle size, zeta potential, surface morphology, drug content, entrapment efficiency and in-vitro drug release. Results: The FT-IR results support that drug have no interaction with excipients, which are used in the preparation of nanoparticle. The particle size, drug content and encapsulation efficiency of the developed nanoparticles ranged from 190 to 255 nm, 80.88% to 94.02%, and 77.12 to 88.74%, respectively. The drug release rate is diffusion-controlled over 8 hours. The F-value for all of the responses shows that the models are significant. The p-value, less than 0.05 for all the responses reveals the significance of the models. Graphical optimisation is done by desirability plot and overlay plot, which contains optimal values of independent variables with the desirability of 1. Conclusion: In conclusion, the results suggested that the optimised lomustine loaded chitosan nanoparticles are useful for brain targeting hence hold the potential for further research and clinical application.

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 Investigating The Retention Potential of Chitosan Nanoparticulate Gel: Design, Development, In Vitro & Ex Vivo Characterization

2020 ◽  
Vol 15 (1) ◽  
pp. 41-67
Author(s):  
Shreya Kaul ◽  
Neha Jain ◽  
Jaya Pandey ◽  
Upendra Nagaich
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Ex Vivo ◽  
Chitosan Nanoparticles ◽  
Entrapment Efficiency ◽  
Eye Drops ◽  
Design Development ◽  
In Vitro Drug Release ◽  
Drug Content

Introduction: The main purpose of the research was to develop, optimize and characterize tobramycin sulphate loaded chitosan nanoparticles based gel in order to ameliorate its therapeutic efficacy, precorneal residence time, stability, targeting and to provide controlled release of the drug. Methods: Box-Behnken design was used to optimize formulation by 3-factors (chitosan, STPP and tween 80) and 3-levels. Developed formulation was subjected for characterizations such as shape and surface morphology, zeta potential, particle size, in vitro drug release studies, entrapment efficiency of drug, visual inspection, pH, viscosity, spreadability, drug content, ex vivo transcorneal permeation studies, ocular tolerance test, antimicrobial studies, isotonicity evaluation and histopathology studies. Results: Based on the evaluation parameters, the optimized formulation showed a particle size of 43.85 ± 0.86 nm and entrapment efficiency 91.56% ± 1.04, PDI 0.254. Cumulative in vitro drug release was up to 92.21% ± 1.71 for 12 hours and drug content was found between 95.36% ± 1.25 to 98.8% ± 1.34. TEM analysis unfolded spherical shape of nanoparticles. TS loaded nanoparticulate gel exhibited significantly higher transcorneal permeation as well as bioadhesion when compared with marketed formulation. Ocular tolerance was evaluated by HET-CAM test and formulation was non-irritant and well-tolerated. Histopathology studies revealed that there was no evidence of damage to the normal structure of the goat cornea. As per ICH guidelines, stability studies were conducted and were subjected for 6 months. Conclusion: Results revealed that the developed formulation could be an ideal substitute for conventional eye drops for the treatment of bacterial keratitis.

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.

Solid Lipid Nanoparticles for Topical Delivery of Acitretin for the Treatment of Psoriasis by Design of Experiment

2020 ◽  
Vol 12 (2) ◽  
pp. 4474-4491
Author(s):  
Rajkumar Aland ◽  
Ganesan M ◽  
P. Rajeswara Rao ◽  
Bhikshapathi D. V. R. N.
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Solid Lipid Nanoparticles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
Tem Analysis ◽  
In Vitro Drug Release ◽  
Solid Lipid

The main objective for this investigation is to develop and optimize the solid lipid nanoparticles formulation of acitretin for the effective drug delivery. Acitretin loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s orthogonal array with eight parameters that could affect the particle size and entrapment efficiency. Based on the results from the analyses of the responses obtained from Taguchi design, three different independent variables including surfactant concentration (%), lipid to drug ratio (w/w) and sonication time (s) were selected for further investigation using central composite design. The  lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. TEM analysis has demonstrated the presence of individual nanoparticles in spherical shape and the results were compatible with particle size measurements.  In vitro drug release of optimized SLN formulation (F2) was found to be 95.63 ± 1.52%, whereas pure drug release was 30.12 after 60 min and the major mechanism of drug release follows first order kinetics release data for optimized formulation (F2) with non-Fickian (anomalous) with a strong correlation coefficient (R2 = 0.94572) of Korsemeyer-Peppas model. The total drug content of acitretin gel formulation was found to 99.86 ± 0.012% and the diameter of gel formulation was 6.9 ± 0.021 cm and that of marketed gel was found to be 5.7 ± 0.06 cm, indicating better spreadability of SLN based gel formulation. The viscosity of gel formulation at 5 rpm was found to be 6.1 x 103 ± 0.4 x 103 cp. The release rate (flux) of acitretin across the membrane and excised skin differs significantly, which indicates about the barrier properties of skin. The flux value for SLN based gel formulation (182.754 ± 3.126 μg cm−2 h−1) was found to be higher than that for marketed gel (122.345 ± 4.786 μg cm−2 h−1). The higher flux and Kp values of SLN based gel suggest that it might be able to enter the skin easily as compared with marketed gel with an advantage of low interfacial tension of the emulsifier film that ensures an excellent contact to the skin. This topically oriented SLN based gel formulation could be useful in providing site-specific dermal treatment of psoriasis

scholarly journals Effect of Chitosan Coating on PLGA Nanoparticles for Oral Delivery of Thymoquinone: In Vitro, Ex Vivo, and Cancer Cell Line Assessments

Coatings ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 6
Author(s):  
Sultan Alshehri ◽  
Syed Sarim Imam ◽  
Md Rizwanullah ◽  
Khalid Umar Fakhri ◽  
Mohd Moshahid Alam Rizvi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Particle Size ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Cancer Cell Line ◽  
Entrapment Efficiency ◽  
Plga Nanoparticles ◽  
Cancer Management ◽  
Mcf 7

In the present study, thymoquinone (TQ)-encapsulated chitosan- (CS)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were formulated using the emulsion evaporation method. NPs were optimized by using 33-QbD approach for improved efficacy against breast cancer. The optimized thymoquinone loaded chitosan coated Poly (d,l-lactide-co-glycolide) nanoparticles (TQ-CS-PLGA-NPs) were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The surface coating of PLGA-NPs was completed by CS coating and there were no significant changes in particle size and entrapment efficiency (EE) observed. The developed TQ-CS-PLGA-NPs showed particle size, polydispersibility index (PDI), and %EE in the range between 126.03–196.71 nm, 0.118–0.205, and 62.75%–92.17%. The high and prolonged TQ release rate was achieved from TQ-PLGA-NPs and TQ-CS-PLGA-NPs. The optimized TQ-CS-PLGA-NPs showed significantly higher mucoadhesion and intestinal permeation compared to uncoated TQ-PLGA-NPs and TQ suspension. Furthermore, TQ-CS-PLGA-NPs showed statistically enhanced antioxidant potential and cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated TQ-PLGA-NPs and pure TQ. On the basis of the above findings, it may be stated that chitosan-coated TQ-PLGA-NPs represent a great potential for breast cancer management.

Mannosylated Solid Lipid Nanocarriers Of Chrysin To Target Gastric Cancer: Optimization and Cell line Study.

2021 ◽  
Vol 18 ◽  
Author(s):  
Sonia S. Pandey ◽  
Farhinbanu I. Shaikh ◽  
Arti R. Gupta ◽  
Rutvi J. Vaidya
Keyword(s):  
Gastric Cancer ◽  
Particle Size ◽  
Ex Vivo ◽  
Biological Effects ◽  
Entrapment Efficiency ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Lipid Nanocarriers

Background: Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability. Objective: The purpose of the present research was to investigate the targeting potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer. Methods: The Chrysin loaded SLNs (C-SLNs) were developed optimized, characterized and further mannosylated. The C-SLNs were developed with high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines. Results: DSC and XRD data predict the chrysin encapsulation in lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in dependent variable - increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs. Conclusion: These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat the gastric cancer.

scholarly journals FORMULATION, OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES FOR SUSTAINED DRUG DELIVERY USING BOX-BEHNKEN DESIGN

2021 ◽  
pp. 216-226
Author(s):  
GEETHA V. S. ◽  
MALARKODI VELRAJ
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Crude Protein ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Box Behnken Design ◽  
Sustained Drug Delivery ◽  
Drug Loading Efficiency

Objective: To formulate, optimize and evaluate 5-fluorouracil loaded liquorice crude protein nanoparticles for sustained drug delivery using Box-Behnken design. Methods: 5-fluorouracil (5-FU) loaded liquorice crude protein (LCP) nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) as stabilizing agent and gluteraldehyde (8% v/v) as cross linking agent. The optimization of prepared nanoparticles was carried out using Box-Behnken design with 3 factors 2 levels and 3 responses. The independent variables were A)5-FU concentration B)LCP concentration and C) sonication time while the responses were R1) Drug entrapment efficiency R2) Drug loading efficiency and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, physicochemical properties like particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, drug loading efficiency and in vitro drug release studies in PBS pH 7.4 (24 h) were carried out. The observed values were found to be in close agreement with the predicted value obtained from the optimization process. Results: 5-fluorouracil loaded LCP nanoparticles were prepared by desolvation method, the optimization was carried out by Box-Behnken design and the final formulation was evaluated for particle size (301.1 nm), zeta-potential (-25.8mV), PDI(0.226), with entrapment efficiency (64.07%), drug loading efficiency (28.54%), in vitro drug release (65.2% in 24 h) respectively. The formulated nanoparticles show Higuchi model drug release kinetics with sustained drug delivery for 24 h in pH7.4 buffer. Conclusion: The results were proved to be the most valuable for the sustained delivery of 5-Fluorouracil using liquorice crude protein as carrier. 5-FU–LCP nanoparticles were prepared using Tween-80 as stabilizing agent and gluteraldehyde as cross-linking agent to possess ideal sustained drug release characteristics.

scholarly journals FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF AN ANTI-MIGRAINE DRUG

2018 ◽  
Vol 8 (5) ◽  
pp. 465-474
Author(s):  
S PADMA PRIYA ◽  
AN Rajalakshmi ◽  
P Ilaveni
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Sodium Alginate ◽  
Release Kinetics ◽  
Drug Loading ◽  
Research Work ◽  
Entrapment Efficiency ◽  
Polyvinyl Pyrrolidone ◽  
Anti Migraine Drug

Objective: The objective of this research work is to develop and evaluate mucoadhesive microspheres of an anti-migraine drug for sustained release. Materials and Methods:  Mucoadhesive microspheres were prepared by emulsification method using Sodium alginate (SA), polyvinyl pyrrolidone (PVP) and Chitosan in the various drug-polymer ratios of 1:1, 1:2 and 1:3. Nine  formulations were formulated and  evaluated for  possible drug polymer interactions, percentage yield, micromeritic properties, particle size, drug content, drug entrapment efficiency, drug loading, swelling index, In-vitro wash off test, in vitro  drug release, surface morphology and release kinetics. Results: The results showed that no significant drug polymer interaction in FTIR studies. Among all the formulations SF3 containing sodium alginate showed 77.18% drug release in 6hrs. Conclusion: Amongst the developed mucoadhesive microspheres, SF3 formulation containing sodium alginate exhibited slow and sustained release in a controlled manner and it is a promising formulation for sustained release of Sumatriptan succinate. Keywords: Mucoadhesive microspheres, Sodium alginate, polyvinyl pyrrolidone, Chitosan, sustained release.

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