Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation

The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.

• Publication year

  2014

• Venue

  BioMed Research International

• Publication date

  2014-07-14

• Fields of study

  Medicine, Materials Science, Chemistry

• Identifiers
  DOI 10.1155/2014/156010PMID 25126544PMCID 4122152
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Optimization of α-tocopherol loaded nanocapsules by the nanoprecipitation method

  2013cited by this paper
• Preparation and optimization of haloperidol loaded solid lipid nanoparticles by Box–Behnken design

  2013cited by this paper
• Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

  2013cited by this paper
• Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

  2013cited by this paper
• In Vitro Evaluation Of The Physicochemical Effects Of Drug Loaded Carbon Nanotubes On Toxicity

  2012cited by this paper
• Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy

  2012cited by this paper
• Current oral and non-oral routes of antiepileptic drug delivery.

  2012cited by this paper
• PLGA-based nanoparticles: an overview of biomedical applications.

  2012cited by this paper
• PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti-tumor activity in BT-549 cells and in vivo evaluation

  2012cited by this paper
• Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies.

  2011cited by this paper
• Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

  2011cited by this paper
• Influence of process conditions on the mean size of PLGA nanoparticles

  2011cited by this paper
• Nanocarrier Aided Nasal Vaccination: An Experimental and Computational Approach

  2011cited by this paper
• Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

  2011cited by this paper
• The Epilepsy Prescriber's Guide to Antiepileptic Drugs: Rufinamide

  2010cited by this paper
• Cyclosporin A Loaded PLGA Nanoparticle: Preparation, Optimization, In-Vitro Characterization and Stability Studies

  2010cited by this paper
• Nanoparticles of Poly(Lactide-Co-Glycolide)-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment

  2010cited by this paper
• Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies.

  2010cited by this paper
• Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery

  2009cited by this paper
• Designing and evaluation of sodium selenite nanoparticles in vitro to improve selenium absorption in ruminants

  2009cited by this paper
• Intranasal Cabergoline: Pharmacokinetic and Pharmacodynamic Studies

  2009cited by this paper
• Sinefungin-PLGA nanoparticles: drug loading, characterization, in vitro drug release and in vivo studies.

  2009cited by this paper
• Parenteral microemulsions: an overview.

  2008cited by this paper
• Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease

  2008cited by this paper
• Preventing β-amyloid fibrillization and deposition: β-sheet breakers and pathological chaperone inhibitors

  2008cited by this paper
• Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis

  2008cited by this paper
• Dual agents loaded PLGA nanoparticles: systematic study of particle size and drug entrapment efficiency.

  2008cited by this paper
• Development and Evaluation of Lorazepam Microemulsions for Parenteral Delivery

  2008cited by this paper
• Alternative splicing of exon 10 in the tau gene as a target for treatment of tauopathies

  2008cited by this paper
• Partition identities and Ramanujan's modular equations

  2007cited by this paper
• Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery.

  2007cited by this paper
• Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: preparation, characterization and in vitro evaluation.

  2007cited by this paper
• Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content.

  2007cited by this paper
• The permeation of nalmefene hydrochloride across different regions of ovine nasal mucosa.

  2006cited by this paper
• PLA/PLGA nanoparticles for sustained release of docetaxel.

  2006cited by this paper
• Thermoanalytical study of praziquantel-loaded PLGA nanoparticles

  2006cited by this paper
• Inclusion Complexation of Lorazepam with Different Cyclodextrins Suitable for Parenteral Use

  2005cited by this paper
• PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution.

  2005cited by this paper
• Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles.

  2005cited by this paper
• Intranasal delivery: An approach to bypass the blood brain barrier

  2004cited by this paper
• Intranasal administration of interferon beta bypasses the blood-brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis.

  2004cited by this paper
• Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles.

  2004cited by this paper
• Solubilizing Excipients in Oral and Injectable Formulations

  2004cited by this paper
• Profiles of methotrexate in blood and CSF following intranasal and intravenous administration to rats.

  2003cited by this paper
• Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating.

  2003cited by this paper
• Biodegradable polymeric nanoparticles as drug delivery devices.

  2001cited by this paper
• Use of ultrasound to prepare lipid emulsions of lorazepam for intravenous injection.

  2001cited by this paper
• Drug release from nanoparticles of Poly(DL-lactide-co-glycolide)

  2000cited by this paper
• Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers.

  1998cited by this paper
• Inclusion Complexation of Lorazepam with β — Cyclodextrin

  1993cited by this paper
• The treatment of epilepsy.

  1948cited by this paper

• Synthesis, Density Functional Theory Analysis and Dissolution Study of Non‐Covalent Derivatives of Modafinil

  2026cites this paper
• Formulation and In-Vitro Evaluation of Lemborexant Orodispersible Film

  2026cites this paper
• Elucidating the Dual Role of Colchicine in Zinc Oxide Nanoparticle Synthesis: A Box–Behnken Design Approach with Structural, Computational, and Antibacterial Evaluation

  2026cites this paper
• ‘Enhancing intranasal transport: levetiracetam-loaded nanospheres journey from nose to brain—optimization via Box–Behnken design and comprehensive in vitro/in vivo assessment’

  2026cites this paper
• Leflunomide loaded transferosomes based hydrogel against rheumatoid arthritis: In Vitro and In Vivo evaluation

  2025cites this paper
• Nanoformulations in epilepsy therapy – a systematic review of emerging strategies in status epilepticus

  2025cites this paper
• OPTIMIZATION FORMULATION OF INSULIN-LOADED POLY-CAPROLACTONE NANOPARTICLES FOR CHRONIC WOUND HEALING USING BOX-BEHNKEN DESIGN

  2025cites this paper
• Design of Experiments (DoE)‐Optimized Polymeric Oxytocin Nanoparticles for Enhanced Nose‐to‐Brain Delivery

  2025cites this paper
• Coated Zein Polymeric Nanoparticles Loaded with Amlodipine as a Repurposed Antibacterial Ocular Cure for MRSA-Induced Infection: Optimization, In Vitro, Ex Vivo, and In Vivo Assessments

  2025cites this paper
• Nose to brain delivery of dapoxetine-loaded PLGA nanoparticle for treatment of premature ejaculation distress in normal and diabetic rats with in silico targeting brain FOX and serotonin proteins.

  2025cites this paper
• Biofabrication, statistical optimization, and characterization of collagen nanoparticles synthesized via Streptomyces cell-free system for cancer therapy

  2025cites this paper
• Folate-Functionalized Polymeric Nanoparticles for 5‑Fluorouracil Delivery to Prostate Cancer: Physicochemical and In Vitro/In Vivo Characterization

  2025cites this paper
• Polymeric nanoparticles for efficient nose-to-brain delivery.

  2025cites this paper
• Emulgel-Based Formulations of Clobetasol Propionate: Formulation Development, Characterization, and Pharmacological Evaluation.

  2025cites this paper
• A process optimization and release modeling of coaxial electrospun aligned core-shell poly (ethylene oxide-poly(l-lactide-co-glycolide)) nanofibers encapsulating nerve growth factor.

  2025cites this paper
• Optimizing a Natural Oil-Based Sertaconazole Nitrate Organogel: enhanced antifungal activity through in vitro and in vivo evaluation

  2025influential citation
• Design, development, and evaluation of magnetic nanoparticles and docetaxel-loaded nanosystem for brain targeting.

  2025cites this paper
• A hydrogel based herbal nanoformulation for enhanced wound healing

  2025cites this paper
• Solid lipid nanoparticles loaded with a novel indole-based multitarget ligand: preparation, characterization, and neuroprotective evaluation in an H₂O₂-induced SH-SY5Y cell model

  2025cites this paper
• Frontiers in therapeutic interventions for epilepsy: nanocarriers as a pivotal catalyst in the synergistic combination of conventional antiepileptics and herbal drugs.

  2024cites this paper
• Synthesis of water-soluble violacein nanoparticles and molecular dynamic study

  2024cites this paper
• DEVELOPMENT AND OPTIMIZATION OF POLYMERIC NANOPARTICLES OF GLYCYRRHIZIN: PHYSICOCHEMICAL CHARACTERIZATION AND ANTIOXIDANT ACTIVITY

  2024cites this paper
• A new evidence-based design-of-experiments approach for optimizing drug delivery systems with exemplification by emulsion-derived Vancomycin-loaded PLGA capsules

  2024cites this paper
• Design, optimization and characterization of atorvastatin loaded chitosan-based polyelectrolyte complex nanoparticles based transdermal patch.

  2024cites this paper
• Recent progress in nanoparticulate-based intranasal delivery for treating of different central nervous system diseases

  2024cites this paper
• Glycerol-silica/chitosan conjugated self-assembled nano-flower framework for Herstulla thompsoni delivery with effectiveness in natural settings: Optimization and pilot scale production.

  2024cites this paper
• The Role of Nanomaterials in Diagnosis and Targeted Drug Delivery

  2024cites this paper
• Formulation of Felodipine lipid nanoparticle-loaded oral fast-dissolving films

  2024cites this paper
• Arg-Specific serine Protease-Targeted edoxaban tosylate monohydrate-Poly (lactic-co-glycolic acid) Nanoparticles: Investigating Stuart-Prower factor targeting and intestinal distribution through Ex-Vivo fluorescent visualization.

  2024cites this paper
• d-α-tocopheryl polyethylene glycol 1000 succinate surface scaffold polysarcosine based polymeric nanoparticles of enzalutamide for the treatment of colorectal cancer: In vitro, in vivo characterizations

  2024cites this paper
• Intranasal Transfersomal Based In Situ Gel for Augmenting Methylphenidate Bioavailability and Brain Delivery: In Vitro and In Vivo Evaluation

  2024cites this paper
• Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

  2024cites this paper
• Bionanofactory for green synthesis of collagen nanoparticles, characterization, optimization, in-vitro and in-vivo anticancer activities

  2024cites this paper
• Challenges and prospects in geriatric epilepsy treatment: the role of the blood–brain barrier in pharmacotherapy and drug delivery

  2024cites this paper
• Valorization of Grape Pomace-Derived Bio-Pesticide via Yeast Capsules- Nano Carriers with Entomotoxic Potential

  2024cites this paper
• Small Particles, Big Potential: Polymeric Nanoparticles for Drug Delivery in Parkinson's Disease

  2024cites this paper
• Mucoadhesive chitosan-poly (lactic-co-glycolic acid) nanoparticles for intranasal delivery of quetiapine - Development & characterization in physiologically relevant 3D tissue models.

  2024cites this paper
• Nose-to-brain drug delivery for the treatment of CNS disease: New development and strategies.

  2023cites this paper
• Nanotechnology for Novel Drug Delivery: A Systematic Review of Classification, Preparation, Characterization, and Applications of Nanoparticles in Drug Delivery

  2023cites this paper
• Formulation and Optimization of Rivastigmine-Loaded PLGA and Chitosan Nanoparticles for Transdermal Delivery

  2023cites this paper
• Fast disintegrating dosage forms of mucoadhesive-based nanoparticles for oral insulin delivery: optimization to in vivo evaluation.

  2023cites this paper
• Tofacitinib Citrate-loaded Nanoparticle Gel for the Treatment of Alopecia Areata: Response Surface Design, Formulation and In vitro-in Vivo Characterization.

  2023cites this paper
• Comparative pharmacodynamic study delineating the efficacy of amantadine loaded nano-emulsified organogel via intranasal versus transdermal route in rotenone-induced Parkinson's disease rat model

  2023cites this paper
• Polysorbate 80 surface modified PLGA nanoparticles: an in-vitro evaluation of cellular uptake and cytotoxicity on neuro-2a cells

  2023cites this paper
• In Vitro Prototyping of a Nano-Organogel for Thermo-Sonic Intra-Cervical Delivery of 5-Fluorouracil-Loaded Solid Lipid Nanoparticles for Cervical Cancer

  2023cites this paper
• Cross-Linked β-Cyclodextrin Based Nanosponges for Allyl Methyl Sulfide Delivery-Physicochemical Characterization and In Vitro Study

  2023cites this paper
• Nanonized carbamazepine for nose-to-brain delivery: pharmaceutical formulation development

  2023cites this paper
• Recent advances in nanotechnology for Intra-nasal drug delivery and clinical applications

  2023cites this paper
• Surface modified biodegradable nanoparticles of Gabapentin. An approach to increase cell uptake

  2023cites this paper
• Fabrication and Evaluation of Polymeric Nanoparticles of Acitretin for the Solubility Enhancement

  2023cites this paper
• Lipase-sensitive fusidic acid polymeric nanoparticles based hydrogel for on-demand delivery against MRSA-infected burn wounds

  2023cites this paper
• Doxorubicin bearing peptide anchored PEGylated PLGA nanoparticles for the effective delivery to prostate cancer cells

  2023cites this paper
• CENTRAL COMPOSITE FACE-CENTERED DESIGN-BASED OPTIMISATION, DEVELOPMENT AND CHARACTERISATION OF FAVIPIRAVIR-LOADED PLGA NANOPARTICLES

  2023cites this paper
• Design, fabrication, optimization and characterization of memantine-loaded biodegradable PLGA nanoscaffolds for treatment of Alzheimer’s disease

  2022influential citation
• Designing of novel nanoemulsions of retinol using box Behnken design for psoriasis

  2022cites this paper
• Genetics of Dravet Syndrome and its Targeted Therapy by Nanomedicine: A Roadmap for Future Treatment of Drug Resistant Seizures.

  2022cites this paper
• Development of nanoemulsion of antiviral drug for brain targeting in the treatment of neuro-AIDS

  2022cites this paper
• Dysfunction of ABC Transporters at the Surface of BBB: Potential Implications in Intractable Epilepsy and Applications of Nanotechnology Enabled Drug Delivery.

  2022cites this paper
• Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

  2022cites this paper
• Development and evaluation of Deferasirox loaded nanoparticles for the treatment of Breast cancer: evaluation in-vitro and cell line study

  2022influential citation
• Sustained release of sulforaphane by bioactive extracellular vesicles for neuroprotective effect on chick model.

  2022cites this paper
• Improvement in Therapeutic Activity and Stability of Neuropeptide Y Using PEGylated Polyplexes in MCF-7 and MDA-MB-231 Cells

  2022cites this paper
• Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study

  2022cites this paper
• Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

  2022cites this paper
• Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

  2022cites this paper
• Enhancing cellular uptake and membrane permeability of gallic acid for breast cancer therapy via folate-tagged PEGylated iron oxide nanoparticles has theronastic agent

  2022cites this paper
• Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

  2022cites this paper
• Effect of Formulation Variables on Fabrication of Risperidone Loaded Nanoparticles for Sustained Drug Delivery

  2022cites this paper
• Process parameter optimization of vitamin D3 loaded Chitosan-TPP nanoparticles

  2022cites this paper
• Fabrication, Optimization, and Evaluation of Paclitaxel and Curcumin Coloaded PLGA Nanoparticles for Improved Antitumor Activity

  2022cites this paper
• In vitro & in vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for baclofen and lamotrigine for neuropathic pain management

  2022cites this paper
• Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

  2022cites this paper
• Apocynin-loaded PLGA nanomedicine tailored with galactosylated chitosan intrigue asialoglycoprotein receptor in hepatic carcinoma: Prospective targeted therapy.

  2022cites this paper
• Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

  2022cites this paper
• Ultrasonic Atomizer-Driven Development of Biocompatible and Biodegradable Poly(d,l-lactide-co-glycolide) Nanocarrier-Encapsulated Suberoylanilide Hydroxamic Acid to Combat Brain Cancer.

  2021cites this paper
• Experimental models for evaluation of direct nose-to-brain drug delivery

  2021cites this paper
• Applications of direct nose-to-brain drug delivery in biomedicine, biotechnology, tissue engineering, and immunology

  2021cites this paper
• In vitro dissolution considerations associated with nano drug delivery systems.

  2021cites this paper
• Zinc Oxide Phytonanoparticles' Effects on Yield and Mineral Contents in Fruits of Tomato (Solanum lycopersicum L. cv. Cherry) under Field Conditions

  2021cites this paper
• PU.1 Mimic Synthetic Peptides Selectively Bind with GATA-1 and Allow c-Jun PU.1 Binding to Enhance Myelopoiesis

  2021cites this paper
• Targeted doxorubicin delivery and release within breast cancer environment using PEGylated chitosan nanoparticles labeled with monoclonal antibodies.

  2021cites this paper
• Curcumin Loaded Eudragit S100/PLGA Nanoparticles in Treatment of Colon Cancer: Formulation, Optimization, and in-vitro Cytotoxicity Study

  2021cites this paper
• Nanomedicines for Brain Drug Delivery

  2021cites this paper
• Pectin co-functionalized dual layered solid lipid nanoparticle made by soluble curcumin for the targeted potential treatment of colorectal cancer.

  2021cites this paper
• BOOSTING THE SKIN DELIVERY OF CURCUMIN THROUGH STEARIC ACID-ETHYL CELLULOSE BLEND HYBRID NANOCARRIERS-BASED APPROACH FOR MITIGATING PSORIASIS

  2021cites this paper
• Biodegradable polymeric nanocarriers for oral delivery of antiretroviral drug: Pharmacokinetic and in vitro permeability studies

  2021cites this paper
• PLGA Nanoparticles in Drug Delivery

  2021cites this paper
• In vitro appraisals and ex vivo permeation prospect of chitosan nanoparticles designed for schizophrenia to intensify nasal delivery

  2021cites this paper
• Design of experiments (DoE) to develop and to optimize nanoparticles as Drug Delivery Systems.

  2021cites this paper
• New Insights into Nanoparticulate Carriers for Direct Nose‐to‐Brain Drug Delivery

  2021cites this paper
• A Novel Sustained Anti-Inflammatory Effect of Atorvastatin—Calcium PLGA Nanoparticles: In Vitro Optimization and In Vivo Evaluation

  2021cites this paper
• Nose to brain delivery of Efavirenz nanosuspension for effective neuro AIDS therapy: in-vitro, in-vivo and pharmacokinetic assessment

  2021cites this paper
• A comparison study of Lipid and Polymeric Nanoparticles in the Nasal Delivery of Meloxicam: Formulation, Characterization, and In-Vitro Evaluation.

  2021cites this paper
• Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier

  2021cites this paper
• TARGETABLE MULTI-DRUG NANOPARTICLES FOR TREATMENT OF GLIOBLASTOMA WITH NEUROIMAGING ASSESSMENT

  2020cites this paper
• Inhalable linezolid loaded PLGA nanoparticles for treatment of tuberculosis: Design, development and in vitro evaluation

  2020cites this paper
• Review Imaging of intranasal drug delivery to the brain

  2020cites this paper
• Fabrication and Characterization of Non-spherical Polymeric Particles

  2020cites this paper
• Development and optimization of dual drug-loaded nanoparticles for the potent anticancer effect on renal carcinoma

  2020cites this paper
• Dual-drugs-loaded polymeric nanoparticles formulation design based on response surface methodology of particle size and zeta potential

  2020cites this paper