Celastrol-loaded liquid crystalline nanoparticles as an anti-inflammatory intervention for the treatment of asthma

Abstract The present study aimed to formulate celastrol into liquid crystalline nanoparticles (LCNPs) through ultrasonication to enhance its therapeutic efficacy in the treatment of asthma. The physiochemical characteristics, in-vitro release studies were determined along with molecular simulations. Celastrol-loaded LCNPs showed the mean particle size of 194.1 ± 9.78 nm and high entrapment efficiency of 99.1 ± 0.02%. TEM revealed cubical-like structure of the nanoparticles and in-vitro release study demonstrated sustained drug release. They also demonstrated significant activity in reducing IL-1β production, when evaluated using immortalized human bronchial epithelial cell lines (BCi-NS1.1), that may help alleviate the symptoms of asthma. Graphical Abstract

[1]  S. Nammi,et al.  Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update , 2020, Inflammopharmacology.

[2]  D. Chellappan,et al.  Patented therapeutic drug delivery strategies for targeting pulmonary diseases , 2020, Expert opinion on therapeutic patents.

[3]  D. Chellappan,et al.  miRNA nanotherapeutics: potential and challenges in respiratory disorders , 2020, Future medicinal chemistry.

[4]  D. Chellappan,et al.  Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases , 2020, Drug development research.

[5]  D. Chellappan,et al.  Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α , 2020, Cancers.

[6]  V. Pillay,et al.  Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma , 2019 .

[7]  D. Chellappan,et al.  Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species. , 2019, Current topics in medicinal chemistry.

[8]  D. Chellappan,et al.  Antibacterial and antioxidant potential of biosynthesized copper nanoparticles mediated through Cissus arnotiana plant extract. , 2019, Journal of photochemistry and photobiology. B, Biology.

[9]  Deeksha,et al.  Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases , 2019, Chemico-Biological Interactions.

[10]  D. Chellappan,et al.  Formulation and characterization of glibenclamide and quercetin-loaded chitosan nanogels targeting skin permeation. , 2019, Therapeutic delivery.

[11]  Deeksha,et al.  Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases. , 2019, Chemico-biological interactions.

[12]  P. Maurya,et al.  Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems. , 2019, Chemico-biological interactions.

[13]  D. Chellappan,et al.  Molecular modulators of celastrol as the keystones for its diverse pharmacological activities. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[14]  V. Pillay,et al.  Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma. , 2018, Colloids and surfaces. B, Biointerfaces.

[15]  G. Canonica,et al.  A Charter to Improve Patient Care in Severe Asthma , 2018, Advances in Therapy.

[16]  D. Chellappan,et al.  Nanotechnology in drug delivery gaining new perspectives in respiratory diseases. , 2018, Panminerva medica.

[17]  V. Pillay,et al.  In silico analytico‐mathematical interpretation of biopolymeric assemblies: Quantification of energy surfaces and molecular attributes via atomistic simulations , 2018, Bioengineering & translational medicine.

[18]  M. R. Mozafari,et al.  Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems , 2018, Pharmaceutics.

[19]  Han‐Gon Choi,et al.  PEGylated polyaminoacid-capped mesoporous silica nanoparticles for mitochondria-targeted delivery of celastrol in solid tumors. , 2018, Colloids and surfaces. B, Biointerfaces.

[20]  D. Chellappan,et al.  Immunological axis of curcumin-loaded vesicular drug delivery systems. , 2018, Future medicinal chemistry.

[21]  O. Abdallah,et al.  Self-assembled phospholipid-based phytosomal nanocarriers as promising platforms for improving oral bioavailability of the anticancer celastrol. , 2018, International journal of pharmaceutics.

[22]  W. Loh,et al.  Liquid crystalline nanoparticles formed by oppositely charged surfactant-polyelectrolyte complexes , 2017 .

[23]  K. Dua,et al.  Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats. , 2017, International journal of biological macromolecules.

[24]  L. Wood,et al.  Mechanisms and treatments for severe, steroid‐resistant allergic airway disease and asthma , 2017, Immunological reviews.

[25]  J. Fonseca,et al.  Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases , 2017, Front. Med..

[26]  V. Velu,et al.  Evaluation of in vitro and in vivo anti-urolithiatic activity of silver nanoparticles containing aqueous leaf extract of Tragia involucrata , 2017, Drug Delivery and Translational Research.

[27]  L. Singh,et al.  Pharmacological evaluation of aqueous extract of syzigium cumini for its antihyperglycemic and antidyslipidemic properties in diabetic rats fed a high cholesterol diet-Role of PPARγ and PPARα. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[28]  C. Rinaldi,et al.  Determining drug release rates of hydrophobic compounds from nanocarriers , 2016, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[29]  H. Dureja,et al.  Development and optimization of boswellic acid-loaded proniosomal gel , 2016, Drug delivery.

[30]  P. Pigram,et al.  Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin , 2015, Nanotechnology, science and applications.

[31]  J. FitzGerald,et al.  Current and emerging treatments for severe asthma. , 2015, Journal of thoracic disease.

[32]  P. Sundaramoorthy,et al.  Enhanced skin permeation of 5α-reductase inhibitors entrapped into surface-modified liquid crystalline nanoparticles , 2015, Archives of pharmacal research.

[33]  M. Mehta,et al.  Proniosomal Gel: A Promising Drug Carrier for Boswellic Acids , 2015 .

[34]  J. Bousquet,et al.  Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation , 2014, International journal of chronic obstructive pulmonary disease.

[35]  Xiaole Qi,et al.  Solid self-microemulsifying dispersible tablets of celastrol: formulation development, charaterization and bioavailability evaluation. , 2014, International journal of pharmaceutics.

[36]  M. Dong,et al.  Thermal properties and nanodispersion behavior of synthesized β-sitosteryl acyl esters: a structure-activity relationship study. , 2013, Journal of colloid and interface science.

[37]  Guoqing Li,et al.  Celastrol Inhibits Lipopolysaccharide-Stimulated Rheumatoid Fibroblast-Like Synoviocyte Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression , 2013, PloS one.

[38]  G. Gopalaswamy,et al.  Influence of foliar spray of nutrients on yield and economics of soybean (Glycine max L. Merill). , 2013 .

[39]  B. Yoo,et al.  Design and In Vitro Evaluation of Finasteride-Loaded Liquid Crystalline Nanoparticles for Topical Delivery , 2012, AAPS PharmSciTech.

[40]  A. Koumbourlis,et al.  Steroid-resistant asthma. , 2012, Paediatric respiratory reviews.

[41]  Quanyin Hu,et al.  Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption , 2012, International journal of nanomedicine.

[42]  S. Parveen,et al.  Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[43]  G. Sethi,et al.  Celastrol inhibits proliferation and induces chemosensitization through down‐regulation of NF‐κB and STAT3 regulated gene products in multiple myeloma cells , 2011, British journal of pharmacology.

[44]  G. Sethi,et al.  Molecular targets of celastrol derived from Thunder of God Vine: potential role in the treatment of inflammatory disorders and cancer. , 2011, Cancer letters.

[45]  A. Salminen,et al.  Celastrol: Molecular targets of Thunder God Vine. , 2010, Biochemical and biophysical research communications.

[46]  P. Howarth,et al.  A new look at the pathogenesis of asthma , 2009, Clinical science.

[47]  Jacob M. Marszalek,et al.  Formulation of Dacarbazine-loaded Cubosomes—Part II: Influence of Process Parameters , 2009, AAPS PharmSciTech.

[48]  D. Jeoung,et al.  Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model. , 2009, European journal of pharmacology.

[49]  Bob Sievers,et al.  Nanomedicine for respiratory diseases. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[50]  S. Johnston,et al.  Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease , 2008, Pharmacology & Therapeutics.

[51]  W. D. de Jong,et al.  Drug delivery and nanoparticles: Applications and hazards , 2008, International journal of nanomedicine.

[52]  Young-Soo Hong,et al.  Inhibition of NF-κB activation through targeting IκB kinase by celastrol, a quinone methide triterpenoid , 2006 .

[53]  M. Henriques,et al.  Inhibition of allergen-induced eosinophil recruitment by natural tetranortriterpenoids is mediated by the suppression of IL-5, CCL11/eotaxin and NFkappaB activation. , 2006, International immunopharmacology.

[54]  F. Tiberg,et al.  Self-assembled lipid superstructures: beyond vesicles and liposomes. , 2005, Nano letters.

[55]  M. Grunstein,et al.  Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle , 2004, European Respiratory Journal.

[56]  J. Reimund,et al.  Celastrol inhibits pro-inflammatory cytokine secretion in Crohn's disease biopsies. , 2004, Biochemical and biophysical research communications.

[57]  J. Calixto,et al.  Anti-inflammatory compounds of plant origin. Part II. modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. , 2004, Planta medica.

[58]  M. Dolovich,et al.  Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. , 2003, British journal of clinical pharmacology.

[59]  I. Pavord,et al.  Management of asthma in adults: current therapy and future directions , 2003, Postgraduate medical journal.

[60]  P. Foster,et al.  Chemokines in asthma: cooperative interaction between chemokines and IL-13. , 2003, The Journal of allergy and clinical immunology.

[61]  Mathias Winterhalter,et al.  Protein encapsulation in liposomes: efficiency depends on interactions between protein and phospholipid bilayer. , 2002, BMC biotechnology.

[62]  J. Renauld.  New insights into the role of cytokines in asthma , 2001, Journal of clinical pathology.

[63]  Kylie A. Williams,et al.  Nanoparticle-Based Drug Delivery for Chronic Obstructive Pulmonary Disorder and Asthma , 2019, Nanotechnology in Modern Animal Biotechnology.

[64]  Kylie A. Williams,et al.  Phytotherapy in Inflammatory Lung Diseases: An Emerging Therapeutic Interventional Approach , 2019, Phytochemistry: An in-silico and in-vitro Update.

[65]  T. G. Singh,et al.  NOVEL DRUG DELIVERY APPROACHES FOR GUGGUL , 2019 .

[66]  Sanyog Jain,et al.  Improved Oral Bioavailability, Therapeutic Efficacy, and Reduced Toxicity of Tamoxifen-Loaded Liquid Crystalline Nanoparticles , 2017, AAPS PharmSciTech.

[67]  S. Ozkan,et al.  Effect of Polymer-Based Nanoparticles on the Assay of Antimicrobial Drug Delivery Systems , 2017 .

[68]  S. Nammi,et al.  Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3)-Induced Memory Impairment in Rats. , 2017, Central nervous system agents in medicinal chemistry.

[69]  S. Satija,et al.  Nanotechnologies for Boswellic Acids , 2014 .

[70]  P. Barnes.  Severe asthma: advances in current management and future therapy. , 2012, The Journal of allergy and clinical immunology.