Improving the efficacy of inhaled drugs in cystic fibrosis: Challenges and emerging drug delivery strategies ☆

Published on Aug 30, 2014in Advanced Drug Delivery Reviews15.47
· DOI :10.1016/J.ADDR.2014.05.008
Ivana d’Angelo19
Estimated H-index: 19
Claudia Conte17
Estimated H-index: 17
+ 3 AuthorsFrancesca Ungaro30
Estimated H-index: 30
Abstract Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians associated with early death. Although the faulty gene is expressed in epithelia throughout the body, lung disease is still responsible for most of the morbidity and mortality of CF patients. As a local delivery route, pulmonary administration represents an ideal way to treat respiratory infections, excessive inflammation and other manifestations typical of CF lung disease. Nonetheless, important determinants of the clinical outcomes of inhaled drugs are the concentration/permanence at the lungs as well as the ability of the drug to overcome local extracellular and cellular barriers. This review focuses on emerging delivery strategies used for local treatment of CF pulmonary disease. After a brief description of the disease and formulation rules dictated by CF lung barriers, it describes current and future trends in inhaled drugs for CF. The most promising advanced formulations are discussed, highlighting the advantages along with the major challenges for researchers working in this field.
📖 Papers frequently viewed together
Several PEGylated polyester-based nanoncologicals have been proposed in the literature, some of them nowadays being under preclinical/clinical trials or marketed. In this review, we describe the main features of PEGylated polyesters and their correspondent nanocarriers. A first part is devoted to intravenously injectable PEGylated nanocarriers, which represent the systems most investigated so far. After describing fundamental design rules dictated by the administration route, PEGylated nanocarri...
#1Amanda G. Oglesby-Sherrouse (UMB: University of Maryland, Baltimore)H-Index: 18
#2Louise Djapgne (UMB: University of Maryland, Baltimore)H-Index: 4
Last. Michael L. Vasil (University of Colorado Denver)H-Index: 27
view all 5 authors...
Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that is refractory to a variety of current antimicrobial therapeutic regimens. Complicating treatment for such infections is the ability of P. aeruginosa to form biofilms, as well as several innate and acquired resistance mechanisms. Previous studies suggest iron plays a role in resistance to antimicrobial therapy, including the efficacy of an FDA-approved iron chelator, deferasirox (DSX), or Gallium, an iron analog, in p...
#1Jung Soo Suk (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 35
#2Anthony J. Kim (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 23
Last. Justin HanesH-Index: 75
view all 11 authors...
Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles...
#1Brian D KentH-Index: 20
#3Edwin J.R. van Beek (Edin.: University of Edinburgh)H-Index: 21
Last. Harm A.W.M. Tiddens (Erasmus University Medical Center)H-Index: 15
view all 6 authors...
Summary Successfully diagnosing concomitant asthma in people with cystic fibrosis (CF) is a challenging proposition, and the utility of conventional diagnostic criteria of asthma in CF populations remains uncertain. Nonetheless, the accurate identification of individuals with CF and asthma allows appropriate tailoring of therapy, and should reduce the unnecessary use of asthma medication in broader CF cohorts. In this review, we discuss the diagnostic challenge posed by asthma in CF, both in ter...
#1Ivana d’AngeloH-Index: 19
#2Claudia ConteH-Index: 17
Last. Francesca UngaroH-Index: 30
view all 5 authors...
Introduction: The application of nanotechnologies to the cancer field for therapeutic, imaging or diagnostic purposes represents an advanced and very attractive approach to overcome the main limits related to conventional chemotherapy. In particular, core–shell nanocarriers can be engineered to provide adequate features to overcome the main biological barriers encountered by free anti-cancer drugs. Areas covered: This review will try to summarise the design rules – as dictated by biological requ...
#1Sabrina Weber (University of Graz)H-Index: 5
#2Andreas Zimmer (University of Graz)H-Index: 8
Last. Jana Pardeike (University of Graz)H-Index: 12
view all 3 authors...
Abstract Drug delivery by inhalation is a noninvasive means of administration that has following advantages for local treatment for airway diseases: reaching the epithelium directly, circumventing first pass metabolism and avoiding systemic toxicity. Moreover, from the physiological point of view, the lung provides advantages for systemic delivery of drugs including its large surface area, a thin alveolar epithelium and extensive vasculature which allow rapid and effective drug absorption. There...
#1Garima Sharma (JIIT: Jaypee Institute of Information Technology)H-Index: 29
#2Saloni Rao (JIIT: Jaypee Institute of Information Technology)H-Index: 1
Last. Reema Gabrani (JIIT: Jaypee Institute of Information Technology)H-Index: 16
view all 6 authors...
Abstract Pseudomonas aeruginosa is a gram-negative pathogen that has become an important cause of infection, especially in patients with compromised host defense mechanisms. It is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteremia. The biofilm formed by the bacteria allows it to adhere to any surface, living or non-living and thus Pseudomonal infections can involve any part of the body. Further, the adaptive and genetic changes of the mi...
#1Anne-Sophie Messiaen (UGent: Ghent University)H-Index: 5
#2Hans J. Nelis (UGent: Ghent University)H-Index: 60
Last. Tom Coenye (UGent: Ghent University)H-Index: 86
view all 3 authors...
Abstract Background Burkholderia cepacia complex (Bcc) organisms produce a wide variety of potential virulence factors, including exopolysaccharides (EPS), and exhibit intrinsic resistance towards many antibiotics. In the present study we investigated the contribution of Bcc biofilm matrix components, including extracellular DNA, cepacian and poly-β-1,6-N-acetylglucosamine, to tobramycin susceptibility. Methods The in vitro bactericidal activity of tobramycin in combination with recombinant huma...
#1Anna Caretti (University of Milan)H-Index: 20
#2Alessandra BragonziH-Index: 36
Last. Paola Signorelli (University of Milan)H-Index: 22
view all 11 authors...
Background Sphingolipids take part in immune response and can initiate and/or sustain inflammation. Various inflammatory diseases have been associated with increased ceramide content, and pharmacological reduction of ceramide diminishes inflammation damage in vivo. Inflammation and susceptibility to microbial infection are two elements in a vicious circle. Recently, sphingolipid metabolism inhibitors were used to reduce infection. Cystic Fibrosis (CF) is characterized by a hyper-inflammation and...
#1Eric W.F.W. Alton (Imperial College London)H-Index: 65
#2A. C. Boyd (Western General Hospital)H-Index: 4
Last. Stephanie G. Sumner-Jones (John Radcliffe Hospital)H-Index: 15
view all 16 authors...
Toxicology study assessing efficacy and safety of repeated administration of lipid/DNA complexes to mouse lung
Cited By67
Last. Hugh D. C. SmythH-Index: 34
view all 3 authors...
#1Santhni Subramaniam (UniSA: University of South Australia)H-Index: 2
#2Paul Joyce (UniSA: University of South Australia)H-Index: 13
Last. Clive A. Prestidge (UniSA: University of South Australia)H-Index: 54
view all 4 authors...
Abstract null null Bacteria have developed a wealth of strategies to avoid and resist the action of antibiotics, one of which involves pathogens invading and forming reservoirs within host cells. Due to the poor cell membrane permeability, stability and retention of conventional antibiotics, this renders current treatments largely ineffective, since achieving a therapeutically relevant antibiotic concentration at the site of intracellular infection is not possible. To overcome such challenges, c...
#1Ling Lin (SYSU: Sun Yat-sen University)H-Index: 6
#2Yixian Zhou (SYSU: Sun Yat-sen University)H-Index: 8
Last. Chuanbin Wu (SYSU: Sun Yat-sen University)H-Index: 33
view all 5 authors...
Abstract null null Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease, and the thick and viscous mucus covering on respiratory epithelia can entrap the inhaled drugs, resulting in compromised therapeutic efficiency. In order to solve this problem, the inhalable ciprofloxacin hydrochloride microparticles (CMs) based on silk fibroin (SF) and mannitol (MAN) were designed and developed. SF was applied to increase the loading efficiency of ciprofloxacin hydrochloride by strong...
#1Yoen-Ju SonH-Index: 15
#2Danforth MillerH-Index: 18
Last. Jeffry G. WeersH-Index: 30
view all 3 authors...
This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug ...
#1Chelsea R. Thorn (UniSA: University of South Australia)H-Index: 5
#2P. Lynne Howell (U of T: University of Toronto)H-Index: 42
Last. Nicky ThomasH-Index: 20
view all 5 authors...
Biofilm-dispersing enzymes degrade the extracellular polymeric matrix surrounding bacterial biofilms, disperse the microbial community and increase their susceptibility to antibiotics and immune cells. Challenges for the clinical translation of biofilm-dispersing enzymes involve their susceptibility to denaturation, degradation, and clearance upon administration in vivo. Drug delivery systems aim to overcome these limitations through encapsulation, stabilization and protection from the exterior ...
#1Salvatore Emanuele Drago (University of Palermo)H-Index: 4
#2Emanuela Fabiola Craparo (University of Palermo)H-Index: 27
Last. Gennara Cavallaro (University of Palermo)H-Index: 44
view all 4 authors...
Abstract null null In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the...
#1Salsabil ElboraieH-Index: 1
Last. Aristides D. TagalakisH-Index: 3
view all 4 authors...
#1Marika Comegna (University of Naples Federico II)H-Index: 10
#2Gemma Conte (Seconda Università degli Studi di Napoli)H-Index: 1
Last. Giuseppe Castaldo (University of Naples Federico II)H-Index: 34
view all 13 authors...
Cystic fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge. In this work, we report the production and characterization of hybrid core–shell nanoparticles (hNPs) comprisi...
#1Yajie Zhang (University of Texas at Austin)H-Index: 7
#2Dan Davis (University of Texas at Austin)H-Index: 14
Last. Robert O. Williams (University of Texas at Austin)H-Index: 63
view all 10 authors...
Abstract Recent advances in formulation sciences have expanded the previously limited design space for biological modalities, including peptide, protein, and vaccine products. At the same time, the discovery and application of new modalities, such as cellular therapies and gene therapies, have presented formidable challenges to formulation scientists. We explore these challenges and highlight the opportunities to overcome them through the development of novel formulations and drug delivery syste...
#1Douweh Leyla Gbian (Laurentian University)H-Index: 1
#2Abdelwahab Omri (Laurentian University)H-Index: 37
Introduction: Cystic fibrosis (CF), is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and affects thousands of people throughout the world. Lung disease ...
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.