Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline. Respir Res 24:112

Division of Allergy and Immunology and Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine and James A, Haley Veteran's Hospital, Tampa, FL 33612, USA.
Respiratory research (Impact Factor: 3.09). 02/2006; 7(1):112. DOI: 10.1186/1465-9921-7-112
Source: PubMed


Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects.
We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma.
A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline.
Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs.
Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system.

11 Reads
  • Source
    • "Furthermore, studies on chitosan nanospheres have shown its cytotoxic effect against various human tumour cell lines (Alpar et al., 2005; Chen et al., 2009; Yang et al., 2009). Recently, chitosan, because of its mucoadhesive properties, was selected as a coating material for PLGA nano-and microparticles when being applied in mucosal administration (Kawashima et al., 2000; Smith et al., 2001; Lee et al., 2006; Malaekeh-Nikouei et al., 2008; Tahara et al., 2010; Zeng et al., 2011). Chitosan presence on the surface was supposed to increase the interaction of the nano-or microparticles with the mucus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The present study reports the preparation and physicochemical characterization of surface-modified poly(lactide-co-glycolide) (PLGA) microparticles containing interleukin-2 (rhIL-2) for pulmonary delivery. The surface of the microparticles was modified with mucoadhesive polymers such as chitosan and Carbopol 971P. The feasibility of this surface modification was confirmed by measuring the zeta potential. Chitosan-modified PLGA microparticles showed a positive zeta potential, while Carbopol-modified PLGA microparticles were negatively charged. The mucin binding efficiency values have shown that the positively charged chitosan coated microparticles showed a higher adhesive percent to the mucin than the negatively charged un-coated or Carbopol 971P coated microparticles. Furthermore, surface modification of microparticles with chitosan and Carbopol 971P has yielded a slight decrease in the amount of protein initially released. These findings suggest the suitability of surface-modified PLGA microparticles as an efficient carrier system for delivery peptides and proteins to the respiratory tract.
    Journal of Microencapsulation 04/2014; 31(4). DOI:10.3109/02652048.2013.858791 · 1.59 Impact Factor
  • Source
    • "Chitosan ENP are also being investigated as anti-allergen therapeutics to treat allergic asthma. For example, theophylline (a drug that reduces the inflammatory effects of allergic asthma) delivered in chitosan ENP (220 AE 23 nm) efficiently blocked experimental allergic asthma by decreasing BAL eosinophilia, bronchial epithelial damage, mucus hypersecretion and lung cell apoptosis (Lee et al., 2006). Imiquimod cream (containing a penetrating agent and a TLR7 agonist that skews immune responses toward the Th1-type) mixed with chitosan ENP (220 AE 23 nm) containing small inhibitory ribonucleic acid specific for the natriuretic peptide receptor A, applied to shaved skin on the backs (above the lung) of mice inhibited AHR, airway eosinophilia, lung histopathology and the Th2 cytokines IL-4 and IL-5 in lung homogenates (Wang et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Engineered nanoparticles (ENP), which could be composed of inorganic metals, metal oxides, metalloids, organic biodegradable and inorganic biocompatible polymers, are being used as carriers for vaccine and drug delivery. There is also increasing interest in their application as delivery agents for the treatment of a variety of lung diseases. Although many studies have shown ENP can be effectively and safely used to enhance the delivery of drugs and vaccines in the periphery, there is concern that some ENP could promote inflammation, with unknown consequences for lung immune homeostasis. In this study, we review research on the effects of ENP on lung immunity, focusing on recent studies using diverse animal models of human lung disease. We summarize how the inflammatory and immune response to ENP is influenced by the diverse biophysical and chemical characteristics of the particles including composition, size and mode of delivery. We further discuss newly described unexpected beneficial properties of ENP administered into the lung, where biocompatible polystyrene or silver nanoparticles can by themselves decrease susceptibility to allergic airways inflammation. Increasing our understanding of the differential effects of diverse types of nanoparticles on pulmonary immune homeostasis, particularly previously underappreciated beneficial outcomes, supports rational ENP translation into novel therapeutics for prevention and/or treatment of inflammatory lung disorders.
    Drug Metabolism Reviews 11/2013; 46(2). DOI:10.3109/03602532.2013.859688 · 5.36 Impact Factor
  • Source
    • "The usefulness of thiolated chitosan (Thio-CS) as a scaffold for controlled drug release has been demonstrated by means of model drugs such as clotrimazole [27], salmon calcitonin [28], insulin [29], and tobramycin [30]. However, most of the research has focused on systemic drug delivery such as neural tissue [31], peroral peptide delivery [32], and nasal administration [33]. Despite the advantages of Thio-CS for tissue engineering, the potential application of this material for bone tissue has not been investigated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for drug delivery. However, its use as a scaffold for bone formation has not been investigated. The aim of this study was to evaluate the potential of Thio-CS in bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study showed that BMP-2 interacted with the Thio-CS and did not affect the swelling behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased osteoblastic cell differentiation but did not show any cytotoxicity until 21 days. Analysis of the in vivo ectopic bone formation at 4 weeks of posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel carrier. Taken together, Thio-CS system might be useful for delivering osteogenic protein BMP-2 and present a promising bone regeneration strategy.
    08/2013; 2013:878930. DOI:10.1155/2013/878930
Show more

Similar Publications

Preview (3 Sources)

11 Reads
Available from