Cyclosporin delivery

Gilger BC, Wilkie DA, Davidson MG, Allen JB. Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis. Am J Vet Res 2001 62 1892-1896. 

Peng, C.C. Chauhan, A. Extended cyclosporine delivery by silicone-hydrogel contact lenses. J. Contr. Release 2011, 154 (3), 161-11 A. 

Nevertheless, there are reports on enhancement of ocular drug absorption by bile salts [33], surfactants [200], and chelators [149], Newton et al. [35] demonstrated that Azone, an enhancer widely tested in transdermal drug delivery [201], increased the ocular absorption of cyclosporine, an immunosuppressant, by a factor of 3, thereby prolonging the survival of a corneal allograft. In 1986, Lee et al. [34] reported that 10 pg/mL cytochalasin B, an agent capable of condensing the actin microfilaments, increased the aqueous humor and iris-ciliary body concentrations of topically applied inulin (5 kDa) by about 70% and 700%, respectively, in the albino rabbit. 

Klyashchitsky, B. A., Owen, A. J., Nebulizer-compatible liquid formulations for aerosol pulmonary delivery of hydrophobic drugs glucocorticoids and cyclosporine,... 

Hebert, M. F., Contributions of hepatic and intestinal P-glycoprotein to cyclosporine and tacrolimus oral drug delivery, Adv. Drug. Del. Rev. 

Taljanski W, Pierzynowski SG, Lundin PD, Westrom BR, Eirefelt S, Podlesny J, Dahlback M, Siwinska Golebiowska H, Karlsson BW (1997) Pulmonary delivery of intratracheally instilled and aerosolized cyclosporine A to young and adult rats. Drug Metab Dispos 25 917-920. 

The use of polymeric nanoparticles in the eye has gained considerable interests in recent years. Ocular disposition, safety, efficacy, and pharmacokinetic profiles of various nanoparticles offer a wide range of application for the delivery of many drugs used to treat common ocular disorders. Polymeric nanoparticles have been utilized to enhance the performance of ibuprofen and cyclosporine, while reducing systemic side effect of carteolol compared with... 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Surfactants are employed in nanoparticle suspensions. Chen et al. (2002) evaluated the pre paration of amorphous nanoparticle suspensions containing cyclosporine A using the evaporative precipitation into aqueous solution (ERAS) system. The effect of particle size was studied varying the drug surfactant ratios, type of surfactants, temperature, drug load, and solvent. Acceptable particle sizes suitable for both oral and parenteral administration were also studied. Additional articles in the nanoparticle delivery of poorly water-soluble drugs include Kipp (2004), Perkins et al. (2000), Young et al. (2000), and Tyner et al. (2004). 

Aliabadi, H. M., A. Mahmud, A. D. Sharifabadi, and A. Lavasanifar. 2005a. Micelles of methoxy poly(ethylene oxide)-tpoly(i -caprolactone) as vehicles for the solubilization and controlled delivery of cyclosporine AJ. Control. Rel.104 301-311. 

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

Takada, K., et al. 1986. Effect of administration route on the selective lymphatic delivery of cyclosporin A by lipid-surfactant mixed micelles. J Pharmacobiodyn 9 156. 

As electroporation is still largely in the experimental stage and may possibly be never used clinically, many workers have employed model nontherapeutic molecules to demonstrate the feasibility of its use, such as sulforhodamine, calcein, and caffeine. However, more therapeutic and biotechnologically derived molecules have now been investigated for transdermal delivery, including, for example, fentanyl [22], metoprolol [21], timolol [36], flurbiprofen [37], cyclosporin [38], heparin [39], oligonucleotides [40], and genes [41]. 

Wang, S., M. Kara, and T.R. Krishnan. 1997. Topical delivery of cyclosporin A co-evaporate using electroporation technique. Drug Dev Ind Pharm 23 657. 

Calvo, P., et al. 1996. Polyester nanocapsules as new topical ocular delivery systems for cyclosporin A. Pharm Res 13 311. 

Tamilvanan, S., et al. 2001. Ocular delivery of cyclosporin A.I. Design and characterization of cyclosporin A-loaded positively charged submicron emulsion. STP Pharm Sci 11 421. 

---