Recent advances in cyclosporine drug delivery: challenges and opportunities

Patel, Dhrumi; Wairkar, Sarika

doi:10.1007/s13346-019-00650-1

Cited by 57 publications

(46 citation statements)

References 103 publications

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“…Thus, the results confirmed that topical administration of CsA by bicontinuous microemulsion was an effective approach to increase drug levels in the skin while decreasing systemic exposure, even though CsA topical use exhibits insufficient percutaneous penetration, owing to hydrophobicity, limited passive diffusion, and high molecular weight (1203 Da, above the suitable size for efficient dermal delivery) [8]. Given the structure of the stratum corneum, efficient drug delivery is still a challenge [9]. Moreover, physiological factors must be considered, for example psoriatic lesions may thicken the stratum corneum and epidermis.…”

Section: Introductionmentioning

confidence: 76%

Improved Dermal Delivery of Cyclosporine A Loaded in Solid Lipid Nanoparticles

et al. 2019

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Cyclosporine A (CsA) is an immunosuppressant frequently used in the therapy of autoimmune disorders, including skin-related diseases. Aiming towards topical delivery, CsA was successfully incorporated into lipid nanoparticles of Lipocire DM and Pluronic F-127 using the hot homogenization method. Two different nanocarriers were optimized: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) where oleic acid was the liquid lipid. The developed nanoparticles showed mean sizes around 200 nm, a negative surface charge, and drug entrapment efficiencies around 85% and 70% for SLNs and NLCs, respectively. The spherical CsA-loaded lipid nanoparticles were stable for 9 weeks when stored at room temperature, and exhibited in vitro pH-dependent release under skin mimetic conditions, following the Peppas–Korsmeyer model. CsA, when loaded in SLNs, was safe to be used up to 140 μg mL−1 in fibroblasts and keratinocytes, while CsA-loaded NLCs and free drug exhibited IC50 values of 55 and 95 μg mL−1 (fibroblasts) and 28 and 30 μg mL−1 (keratinocytes), respectively. The developed SLNs were able to retain the drug in pork skin with a reduced permeation rate in relation to NLCs. These findings suggest that SLNs are a potential alternative to produce stable and safe CsA nanocarriers for topical administration.

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Section: Introductionmentioning

confidence: 76%

Improved Dermal Delivery of Cyclosporine A Loaded in Solid Lipid Nanoparticles

et al. 2019

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“…Furthermore ciclosporin blocks both the p38 and c-Jun N-terminal kinase (JNK) pathways in addition to calcineurin-blocking activity [48]. JNK and p38 work in the stress response like inflammation and apoptosis [49][50][51]. The corticosteroid agents inhibit the arachidonic acid pathway indirectly through the induction of lipocortin synthesis, which inhibits the phospholipase A2 enzyme, therefore preventing the production of all proinflammatory mediators, including the arachidonic acid cited above [1,35,41].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Section: Mechanism Of Actionmentioning

confidence: 99%

Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation

et al. 2020

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Ocular inflammation is one of the most common symptom of eye disorders and diseases. The therapeutic management of this inflammation must be rapid and effective in order to avoid deleterious effects for the eye and the vision. Steroidal (SAID) and non-steroidal (NSAID) anti-inflammatory drugs and immunosuppressive agents have been shown to be effective in treating inflammation of the ocular surface of the eye by topical administration. However, it is well established that the anatomical and physiological ocular barriers are limiting factors for drug penetration. In addition, such drugs are generally characterized by a very low aqueous solubility, resulting in low bioavailability as only 1% to 5% of the applied drug permeates the cornea. The present review gives an updated insight on the conventional formulations used in the treatment of ocular inflammation, i.e., ointments, eye drops, solutions, suspensions, gels, and emulsions, based on the commercial products available on the US, European, and French markets. Additionally, sophisticated formulations and innovative ocular drug delivery systems will be discussed. Promising results are presented with micro- and nanoparticulated systems, or combined strategies with polymers and colloidal systems, which offer a synergy in bioavailability and sustained release. Finally, different tools allowing the physical characterization of all these delivery systems, as well as in vitro, ex vivo, and in vivo evaluations, will be considered with regards to the safety, the tolerance, and the efficiency of the drug products.

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“…In addition, DMSO is yet to be approved for formulation to allow for oral or other delivery systems [22]. However, Neoral is an FDA-approved cyclosporine microemulsion formulation for oral use and Restasis is a topical application for ophthalmic use [23]. Therefore, we can assume that it is safer to use a microemulsion for clinical use as a drug delivery vehicle than DMSO even though the long-term use of DMSO as a solvent for drug delivery remains a safety concern.…”

Section: Introductionmentioning

confidence: 99%

CYP3A Excipient-Based Microemulsion Prolongs the Effect of Magnolol on Ischemia Stroke Rats

2020

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Magnolol, which is a CYP3A substrate, is a well-known agent that can facilitate neuroprotection and reduce ischemic brain damage. However, a well-controlled release formulation is needed for the effective delivery of magnolol due to its poor water solubility. In this study, we have developed a formulation for a CYP3A-excipient microemulsion, which can be administrated intraperitoneally to increase the solubility and bioavailability of magnolol and increase its neuroprotective effect against ischemic brain injury. The results showed a significant improvement in the area under the plotted curve of drug concentration versus time curve (AUC0–t) and mean residence time (MRT) of magnolol in microemulsion compared to when it was dissolved in dimethyl sulfoxide (DMSO). Both magnolol in DMSO and microemulsion, administrated after the onset of ischemia, showed a reduced visual brain infarct size. As such, this demonstrates a therapeutic effect on ischemic brain injury caused by occlusion, however it is important to note that a pharmacological effect cannot be concluded by this study. Ultimately, our study suggests that the excipient inhibitor-based microemulsion formulation could be a promising concept for the substrate drugs of CYP3A.

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Recent advances in cyclosporine drug delivery: challenges and opportunities

Cited by 57 publications

References 103 publications

Improved Dermal Delivery of Cyclosporine A Loaded in Solid Lipid Nanoparticles

Improved Dermal Delivery of Cyclosporine A Loaded in Solid Lipid Nanoparticles

Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation

CYP3A Excipient-Based Microemulsion Prolongs the Effect of Magnolol on Ischemia Stroke Rats

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