Development of softgel capsules containing cyclosporine a encapsulated pine essential oil based self-microemulsifying drug delivery system

Cyclosporine (CsA) has a selective property of suppressing various T-lymphocyte functions. This is of utmost importance in preventing allograft rejection by several organ transplantations, as well as in the treatment of systemic and local autoimmune disorders. However, the poor water solubility of CsA can be a major hurdle for its absorption into the blood stream, which leads to low bioavailability and thus less efficacy. The aim of this study was to prepare, characterize, and evaluate in vitro as well as in vivo, the potential of the innovative CsA drug delivery system. The latter contains CsA in spherical amorphous solid dispersion (SASD) which is embedded in an original α-cyclodextrin and β-cyclodextrin polymer mixture (Poly-αβ-CD) as a multifunctional amorphous carrier. The new developed SASD formulation showed that CsA was molecularly dispersed in αβ-cyclodextrins in an amorphous form, as was confirmed by physicochemical characterization studies. Interestingly, the peptide secondary structure, and thus, the drug activity was not impacted by the preparation of SASD as was shown by circular dichroism. Furthermore, the in vitro CsA release profile kinetics was almost identical to the commercially available product Neoral®. This study presents the first in vivo proof-of-concept for a novel drug delivery system based on Poly-αβ-CD containing CsA, with SASD allowing for increased bioavailibility. The pharmacokinetic parameters of cyclosporine A from the spherical spray-dried dispersion formulation was demonstrated in a “rat” animal model. For comparison, the commercially available Neoral® was studied. Importantly, the pharmacokinetic parameters were improved by extending Tmax from 2 to 3 h after the oral administration in rats, and eventually preventing the enterohepatic circulation. All these results clearly demonstrate the improved pharmacokinetic parameters and enhanced bioavailability of CsA in the new developed drug delivery system. These data demonstrated the superiority of the newly developed Poly-αβ-CD formulation for oral administration of the poorly soluble CsA in vivo without altering its secondary structure. Poly-αβ-CD can be a very useful tool for the oral administration of poorly water-soluble drugs.

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Novel Drug Delivery System from Essential Oil ofTrachyspermum ammi

LS International Journal of Life Sciences ◽

10.5958/2319-1198.2015.00001.9 ◽

2015 ◽

Vol 4 (1) ◽

pp. 1

Author(s):

Priya Tomar ◽

C.P. Malik

Keyword(s):

Drug Delivery ◽

Essential Oil ◽

Drug Delivery System ◽

Delivery System ◽

Novel Drug Delivery System ◽

Novel Drug

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Cyclosporine A Drug-Delivery System for High-risk Keratoplasty

Ophthalmology ◽

10.1016/j.ophtha.2013.06.007 ◽

2013 ◽

Vol 120 (9) ◽

pp. e65-e66 ◽

Cited By ~ 2

Author(s):

Jiaxu Hong ◽

Zuguo Liu ◽

Xinghuai Sun ◽

Jianjiang Xu

Keyword(s):

Drug Delivery ◽

High Risk ◽

Drug Delivery System ◽

Delivery System ◽

Cyclosporine A

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pH-Responsive Alginate-Based Microparticles for Colon-Targeted Delivery of Pure Cyclosporine A Crystals to Treat Ulcerative Colitis

Pharmaceutics ◽

10.3390/pharmaceutics13091412 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1412

Author(s):

Murtada A. Oshi ◽

Juho Lee ◽

Jihyun Kim ◽

Nurhasni Hasan ◽

Eunok Im ◽

...

Keyword(s):

Ulcerative Colitis ◽

Drug Delivery ◽

Side Effects ◽

Drug Delivery System ◽

Delivery System ◽

Cyclosporine A ◽

Targeted Delivery ◽

Drug Loading ◽

Systemic Absorption ◽

Systemic Side Effects

Cyclosporine A (CsA) is a potent immunosuppressant for treating ulcerative colitis (UC). However, owing to severe systemic side effects, CsA application in UC therapy remains limited. Herein, a colon-targeted drug delivery system consisting of CsA crystals (CsAc)-loaded, Eudragit S 100 (ES)-coated alginate microparticles (CsAc-EAMPs) was established to minimize systemic side effects and enhance the therapeutic efficacy of CsA. Homogeneously-sized CsAs (3.1 ± 0.9 μm) were prepared by anti-solvent precipitation, followed by the fabrication of 47.1 ± 6.5 μm-sized CsAc-EAMPs via ionic gelation and ES coating. CsAc-EAMPs exhibited a high drug loading capacity (48 ± 5%) and a CsA encapsulation efficacy of 77 ± 9%. The in vitro drug release study revealed that CsA release from CsAc-EAMPs was suppressed under conditions simulating the stomach and small intestine, resulting in minimized systemic absorption and side effects. Following exposure to the simulated colon conditions, along with ES dissolution and disintegration of alginate microparticles, CsA was released from CsAc-EAMPs, exhibiting a sustained-release profile for up to 24 h after administration. Given the effective colonic delivery of CsA molecules, CsAc-EAMPs conferred enhanced anti-inflammatory activity in mouse model of dextran sulfate sodium (DSS)-induced colitis. These findings suggest that CsAc-EAMPs is a promising drug delivery system for treating UC.

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A Novel Cyclosporine A Drug-Delivery System for Prevention of Human Corneal Rejection after High-risk Keratoplasty: A Clinical Study

Ophthalmology ◽

10.1016/j.ophtha.2012.09.035 ◽

2013 ◽

Vol 120 (4) ◽

pp. 695-702 ◽

Cited By ~ 15

Author(s):

Weiyun Shi ◽

Min Chen ◽

Lixin Xie ◽

Mingna Liu ◽

Hua Gao ◽

...

Keyword(s):

Drug Delivery ◽

Clinical Study ◽

High Risk ◽

Drug Delivery System ◽

Delivery System ◽

Cyclosporine A

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Combination of Nanomicellar Technology and In Situ Gelling Polymer as Ocular Drug Delivery System (ODDS) for Cyclosporine-A

Pharmaceutics ◽

10.3390/pharmaceutics13020192 ◽

2021 ◽

Vol 13 (2) ◽

pp. 192

Author(s):

Eleonora Terreni ◽

Erica Zucchetti ◽

Silvia Tampucci ◽

Susi Burgalassi ◽

Daniela Monti ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Cyclosporine A ◽

Sol Gel ◽

Ocular Drug Delivery ◽

Water Soluble ◽

Glycol Succinate ◽

In Situ Gelling

A combination of in situ gelling systems and a loaded drug self-assembling nanomicellar carrier was chosen in this study as a new potential Ocular Drug Delivery System (ODDS) for Cyclosporine-A (CyA), a poorly water-soluble drug. Two non-ionic surfactants (d-α-tocopherol polyethylene glycol succinate, VitE-TPGS and polyoxyl 40 hydrogenated castor oil, RH-40) were used to produce the nanomicelles. The physical–chemical characterization of the nanomicelles in terms of CyA entrapment (EE%) and loading efficiency (LE%), cloud point (CP), regeneration time (RT), size and polydispersity index (PI) allowed us to select the best combination of surfactant mixture, which showed appropriate stability, high CyA-EE (99.07%), very small and homogeneous dimensions and favored the solubilization of an amount of CyA (0.144% w/w) comparable to that contained in marketed emulsion Ikervis®. The selected nanomicellar formulation incorporated into optimized ion-sensitive polymeric dispersions of gellan gum (GG-LA: 0.10, 0.15 and 0.20% w/w) able to trigger the sol–gel transition after instillation was characterized from technological (osmolality, pH, gelling capacity, rheological behavior, wettability, TEM and storage stability at 4 and 20 °C) and biopharmaceutical points of view. This new combined approach allowed us to obtain clear aqueous dispersions that were easy to instill and able to form a viscous gel when in contact with the tear fluid, improving CyA ocular bioavailability. Furthermore, this new ODDS prevented CyA transcorneal permeation, exhibited low cytotoxicity and prolonged the CyA resident time in the precorneal area compared to Ikervis®.

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