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Low-molecular-weight heparin (LMWH)-loaded large porous PEG-PLGA particles for the treatment of asthma.

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.


CONCLUSION
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.