Advanced delivery of Ciclosporin A: present state and perspective

Abstract

Ciclosporin A has been used as an immunosuppressor for organ transplantation and other autoimmune disorders for a number of years. Its poor biopharmaceutical characteristics of low solubility and permeability makes the uphill task of designing delivery systems even more challenging for the drug delivery scientist. Works have been performed to investigate administration through various body routes, and have employed approaches that use as emulsions, microspheres, nanoparticles, liposomes, physical and chemical penetration enhancers. Although progress has been made, there is still room for improvement in the application of ciclosporin A, as none of these formulations is ideal.

Immunosuppressive and anti‐inflammatory properties of engineered nanomaterials

“…The fungal peptide cyclosporine A and the bacterial macrolide lactone tacrolimus, approved by the US FDA in 1983 and 1994, respectively, are widely used in transplant medicine and for treatment of autoimmune disorders (Liu et al, 2007). Cyclosporine A and tacrolimus both interfere with activity of calcineurin, a factor critical for activation of the transcription factor, nuclear factor of activated T-cells, thus preventing transcription of genes encoding cytokines and decreasing the rate of graft rejection (Abbas et al, 2012 ).…”

“…Cyclosporine A and tacrolimus both interfere with activity of calcineurin, a factor critical for activation of the transcription factor, nuclear factor of activated T-cells, thus preventing transcription of genes encoding cytokines and decreasing the rate of graft rejection (Abbas et al, 2012 ). Common side effects from these agents include kidney damage, cardiotoxicity and high BP (Bottiger et al, 1999;Liu et al, 2007). Their poor solubility in water, low bioavailability and high inter-patient variability in Table 1 Reformulation of traditional immunosuppressive and anti-inflammatory drugs into nanotechnology platforms…”

“…metabolism and excretion render dose monitoring of these drugs difficult (Bottiger et al, 1999;Liu et al, 2007). Some of these challenges may be circumvented by formulating the immunosuppressants into nanoparticles (Canadas et al, 2004;Liu et al, 2007;Czogalla, 2009;Shin et al, 2010;Pople and Singh, 2012;Tammam et al, 2012).…”

“…Some of these challenges may be circumvented by formulating the immunosuppressants into nanoparticles (Canadas et al, 2004;Liu et al, 2007;Czogalla, 2009;Shin et al, 2010;Pople and Singh, 2012;Tammam et al, 2012). For example, liposomal and polymeric nanoparticle reformulation of cyclosporine significantly reduced nephrotoxicity of the drug in rats and in a rat ischaemic kidney model (Freise et al, 1994;Italia et al, 2007).…”

The Oral Delivery of Proteins Using Interpolymer Polyelectrolyte Complexes

“…This is due to a number of factors including their structural complexity and sensitivity to degradation, as well as the numerous barriers to oral absorption [1-3,7-10]. When administered orally, the bioavailability of most proteins is virtually zero [5], exceptions being the hydrophobic immunosuppressive cyclosporin A [10,11] and the analogue of vasopressin, desmopressin acetate [1,12]. It is thought that nonparenteral administration will increase patient compliance, which may be particularly pertinent in the case for patients who have a phobia of needles [1,5,10].…”