Drug and Alcohol Rehabilitation: The Combined Use of Paclitaxel-Loaded Nanoparticles With a Low-Molecular-Weight Copolymer Inhibitor of P-Glycoprotein to Overcome Drug Resistance.
The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance.
Filed under: Drug and Alcohol Rehabilitation
Int J Nanomedicine. 2013; 8: 379-91
Wan CP, Letchford K, Jackson JK, Burt HM
Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically “frozen core” structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin-Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.
HubMed – drug
Characterization and stability studies of a novel liposomal cyclosporin A prepared using the supercritical fluid method: comparison with the modified conventional Bangham method.
Filed under: Drug and Alcohol Rehabilitation
Int J Nanomedicine. 2013; 8: 365-77
Karn PR, Cho W, Park HJ, Park JS, Hwang SJ
A novel method to prepare cyclosporin A encapsulated liposomes was introduced using supercritical fluid of carbon dioxide (SCF-CO(2)) as an antisolvent. To investigate the strength of the newly developed SCF-CO(2) method compared with the modified conventional Bangham method, particle size, zeta potential, and polydispersity index (PDI) of both liposomal formulations were characterized and compared. In addition, entrapment efficiency (EE) and drug loading (DL) characteristics were analyzed by reversed-phase high-performance liquid chromatography. Significantly larger particle size and PDI were revealed from the conventional method, while EE (%) and DL (%) did not exhibit any significant differences. The SCF-CO(2) liposomes were found to be relatively smaller, multilamellar, and spherical with a smoother surface as determined by transmission electron microscopy. SCF-CO(2) liposomes showed no significant differences in their particle size and PDI after more than 3 months, whereas conventional liposomes exhibited significant changes in their particle size. The initial yield (%), EE (%), and DL (%) of SCF-CO(2) liposomes and conventional liposomes were 90.98 ± 2.94, 92.20 ± 1.36, 20.99 ± 0.84 and 90.72 ± 2.83, 90.24 ± 1.37, 20.47 ± 0.94, respectively, which changed after 14 weeks to 86.65 ± 0.30, 87.63 ± 0.72, 18.98 ± 0.22 and 75.04 ± 8.80, 84.59 ± 5.13, 15.94 ± 2.80, respectively. Therefore, the newly developed SCF-CO(2) method could be a better alternative compared with the conventional method and may provide a promising approach for large-scale production of liposomes.
HubMed – drug
The safety of long-acting ?(2)-agonists in the treatment of stable chronic obstructive pulmonary disease.
Filed under: Drug and Alcohol Rehabilitation
Int J Chron Obstruct Pulmon Dis. 2013; 8: 53-64
Decramer ML, Hanania NA, Lötvall JO, Yawn BP
Inhaled long-acting bronchodilators are the mainstay of pharmacotherapy for chronic obstructive pulmonary disease (COPD). Both the twice-daily long-acting ?(2)-adrenoceptor agonists (LABAs) salmeterol and formoterol and the once-daily LABA indacaterol are indicated for use in COPD. This review examines current evidence for the safety of LABAs in COPD, focusing on their effect on exacerbations and deaths.We searched PubMed for placebo-controlled studies evaluating long-term (?24 weeks) use of formoterol, salmeterol, or indacaterol in patients with stable COPD, published between January 1990 and September 2012. We summarized data relating to exacerbations and adverse events, particularly events related to COPD.From 20 studies examined (8774 LABA-treated patients), there was no evidence of an association between LABA treatment and increased exacerbations, COPD-related adverse events, or deaths. Where analyzed as an efficacy outcome, LABA treatment was generally associated with significant or numerical reductions in COPD exacerbations compared with placebo. Incidences of COPD-related adverse events were similar for active and placebo treatments. The incidence of adverse events typically associated with the ?(2)-agonist drug class such as skeletal muscle tremors and palpitations was low (often <1% of patients), and there were no reports of increased incidence of cardiac arrhythmias. The systemic effects of ?(2)-adrenoceptor stimulation, such as high glucose and potassium levels, were considered minor.Current evidence from clinical studies of the safety and tolerability profile of LABAs supports their long-term use in COPD. HubMed – drug
A challenge to the seven widely believed concepts of COPD.
Filed under: Drug and Alcohol Rehabilitation
Int J Chron Obstruct Pulmon Dis. 2013; 8: 21-30
Al-Kassimi FA, Alhamad EH
THIS REVIEW PROPOSES A CRITICAL REASSESSMENT (BASED ENTIRELY ON PUBLISHED EVIDENCE) OF THE FOLLOWING SEVEN COMMON BELIEFS ABOUT CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): (1) COPD is one disease. (2) There is a valid definition for COPD. (The current definition includes cases of irreversible asthma and bronchiectasis, and occasionally, other obstructive lung conditions). (3) Irreversible asthma in smokers and COPD cannot be differentiated. (4) A “chronic bronchitis” form of COPD exists and is characterized by blue bloater status and normal carbon monoxide diffusion studies. (5) Phenotyping has no bearing on medication choice in COPD. (6) Computerized scoring of lung attenuation on CT scans can diagnose emphysema. (Emphysema scores overlap in irreversible asthma and COPD); however, qualitative visual changes may be useful for differentiation. (7) A definable entity called the overlap (of COPD and asthma) syndrome exists. Conflict over the abovementioned points denies patients proper phenotype-guided therapy and encourages a multidrug approach to COPD management. The recently coined term, overlap syndrome, invites a double-barreled therapy aimed at asthma and COPD, despite the absence of any agreement about how to define the syndrome and the lack of any related drug trials (in the area of inhaled corticosteroids). A diagnosis of COPD is associated with high morbidity and escalating costs, suggesting the need for a thorough new examination of the evidence.
HubMed – drug
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