Formulation Strategy for the Delivery of Cyclosporine A: Comparison of Two Polymeric Nanospheres

Abstract

A wide range of nanoparticles has been explored for the delivery of highly hydrophobic drugs, but very few publications provide comparative data of the performance of different nanoparticles. To address this need, this publication compares poly(lactic-co-glycolic acid) (PLGA) nanoparticles and nanospheres made from tyrosine-derived tri-block copolymers (termed TyroSpheres) for their respective performance as carriers for cyclosporine A (CSA). Using previously reported data on PLGA, we followed similar experimental protocols to evaluate the in vitro characteristics of TyroSpheres. Although there are some similarities between the two particle systems for the delivery of CSA, such as effective encapsulation and epidermal skin penetration, several differences were notable. First, the methods of preparation were different, i.e., self-assembly and emulsion-diffusion-evaporation process for TyroSpheres and PLGA, respectively. Second, TyroSpheres provided 7-day diffusion-controlled release, whereas PLGA nanoparticles provided >21-day erosion-controlled release. Third, the size of TyroSpheres was measured to be ~60–70 nm irrespective of drug loading, whereas the size of PLGA nanoparticles (~100–250 nm) was dependent on drug loading and the method of preparation. Overall, this publication provides a direct comparison between two different types of nanoparticles and illuminates the respective advantages and disadvantages, using CSA as a model for the release of highly hydrophobic drugs.

Nanoparticles and nanofibers for topical drug delivery

“…Batheja et al demonstrated that a gel formulation of TyroSpheres loaded with Nile red (a hydrophobic model drug) significantly enhanced skin permeation (1.4–1.8 fold) compared to an aqueous dispersion of Nile red-loaded TyroSpheres, both in vitro and in vivo [31]. As these TyroSpheres are suitable only for hydrophobic drugs, they have been extensively studied for the binding and delivery of various therapeutic agents that are hydrophobic and water-insoluble, for example curcumin (unpublished data), cyclosporine A [32], sildenafil [33], rolipram [34] and paclitaxel [30,35,36]. Moreover, these nanospheres are stable for about 6 months, after which time they degrade, most likely through hydrolysis of their ester bonds [28].…”

“…Drug release from TyroSpheres is dependent on the properties of the drug, the binding and loading efficiencies, and the pH of the solution [37]. For example, Goyal et al showed that the release of cyclosporine A was inversely proportional to the amount of drug loaded in the TyroSpheres [32]. …”

“…This medium should be biocompatible and used to facilitate percutaneous absorption. The suspending medium may also alter the release kinetics of the drug from the nanoparticles [32]. A recent review highlights the considerations employed for the development of topical dermatologic formulations [180].…”

Polymeric nanospheres for topical delivery of vitamin D3

“…The drug-loaded TyroSpheres showed reproducible hydrodynamic diameter of approximately 70 nm and low polydispersity index (0.17), making this polymer the lead candidate evaluated for nanosphere applications (Sheihet et al, 2005). TyroSpheres have been previously evaluated for topical delivery of lipophilic drug/dye molecules (Nile Red (Batheja, 2011 #159), paclitaxel (Kilfoyle et al, 2012), cyclosporine A (Goyal et al, 2015), and adapalene (Ramezanli et al, 2016)) to treat dermatological diseases such as psoriasis and acne. Additionally, theses nanocarriers were able to localize in the hair follicles and release the drug in the pilosebaceous unit (Ramezanli et al, 2016).…”

Grooved Glaucoma Drainage Devices That Continuously Deliver Cyclosporine A Decrease Postsurgical Scar Formation in Rabbit Eyes

“…Several drug delivery systems capable of sustained release of CsA have been developed, including hydrogel contact lens, 12,13 microspheres, 14 nanoparticles, 15,16 sol-gel, 17 and micelles, 18 some of which may also be used in combination. 19 In our recently published paper, we developed a novel GDD coated with CsA and poly (lactic-co-glycolic acid) polymer (CsA-PLGA) for continuous drug delivery in order to prevent scar formation after glaucoma surgery.…”