title: Low-molecular-weight heparin (LMWH)-loaded large porous PEG-PLGA particles for the treatment of asthma.
abstract: BACKGROUND
  Heparin-like compounds interrupt leukocyte adhesion and migration, and prevent release of chemical mediators during the process of inflammation. However, little is known whether the anti-inflammatory property of smaller heparin fragments, low-molecular-weight heparin (LMWH), plays any role in the process of airway inflammation. In this study, we sought to evaluate the efficacy of LMWH-loaded large porous polyethylene glycol-poly(D,L-lactide-co-glycolide) (PEG-PLGA) particulate formulations in alleviating the cellular and biochemical changes associated with asthma.
  
  
  METHODS
  To study the pharmacological efficacy of LMWH for the treatment of asthma, we have used a previously optimized polymeric formulation of LMWH. The anti-asthmatic efficacy of the optimized formulation was studied in an ovalbumin-sensitized rat model of asthma. The influence of the formulation on asthmatic lungs was assessed by measuring the total protein content and number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Lungs were also examined for morphological and structural changes that may occur in asthmatic lungs.
  
  
  RESULTS
  Compared with healthy animals, asthmatic animals showed a seven- and threefold increase in the protein content and number of inflammatory cells in BALF, respectively. However, intratracheal LMWH particles reduced the protein content by 2.5-fold and the number of inflammatory cells by 1.8-fold-comparable to those of sham animals. Similarly, LMWH particles reduced the lactate dehydrogenase levels by 2.8- and threefold in BALF and plasma, respectively. The airway wall thickness also decreased from 47.37±6.02 μm to 21.35±3.60 μm upon treatment with PEG-PLGA particles of LMWH. Goblet cell hyperplasia was also reduced in asthmatic rats treated with LMWH particles.
  
  
  CONCLUSIONS
  PLGA particles of LMWH were efficacious in improving cellular and histological changes associated with asthma, and thus this polymeric formulation has the potential for further development into a clinically viable anti-asthma therapy.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center , Amarillo, TX 79106.
authors.forename: Brijeshkumar
authors.initials: B
authors.lastname: Patel
authors.forename: Nilesh
authors.initials: N
authors.lastname: Gupta
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D000280:Administration, Inhalation; D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000737:chemistry; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D010047:Ovalbumin; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D006495:Heparin, Low-Molecular-Weight; D018836:Inflammation Mediators; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D010047:Ovalbumin