Employing a PLGA-TPGS based nanoparticle to improve the ocular delivery of Acyclovir

Abstract

Delivering drugs via the ocular route has always been a challenge for poorly soluble drugs. The various anatomical and physiological barriers in the eye cavity hinder the residence of drugs within the corneal and precorneal regions. In this study, the nanosystem that could sufficiently deliver the poorly soluble Acyclovir topically via ocular route. Our nanosystem is composed of the biocompatible PLGA polymer stabilized with TPGS which possess a high emulsifying capacity and is also known as P-gp inhibitor. The optimized nanoparticles were prepared with 0.3% TPGS and had particle-size of 262.3 nm, zeta-potential of +15.14 mV. The physicochemical-characterization, ex vivo transcorneal permeation, ocular-irritation and Acyclovir ocular-availability, following topical ocular application of PLGA-NPs in rabbit eyes, were performed. The tested parameters and irritation by Draize’s test suggested the suitability and safety of PLGA-NPs for ocular use. An ultrahigh performance liquid chromatographic method was developed, validated, and applied to quantify Acyclovir in aqueous humor which was shown to be significantly higher (p < 0.05) using the developed nanoparticles as compared to Acyclovir-aqueous suspension following their single topical ocular administration. Noticeable 2.78-, 1.71- and 2.2-times increased values of AUC0–24h, t1/2 (h) and MRT0–24h were found, respectively, with the PLGA-TPGS-NPs as compared to ACY-AqS. These results demonstrate the superiority of delivering Acyclovir using a nanosystem compared to conventional methods.

Development of nanoparticle-delivery systems for antiviral agents: A review

“…The ability of PLGA-TPGS nanoparticles to overcome the barriers associated with the ocular delivery of the antiviral agent acyclovir have been investigated [ 5 ]. Here, PLGA (poly(lactic- co -glycolic acid)) is a biodegradable polymer and TPGS (D-α-Tocopherol polyethylene glycol 1000 succinate) is a synthetic surface-active material that releases vitamin E to cell membranes.…”

PEGylated Lipid Polymeric Nanoparticle–Encapsulated Acyclovir for In Vitro Controlled Release and Ex Vivo Gut Sac Permeation

“…Amount of encapsulated ACV in nanoparticles was identified indirectly in high-performance liquid chromatography (HPLC) (24). Agilent 1260 Series HPLC system fitted with a photodiode array detector (DAD), and use Thermo Fisher Syncronis C-18 (5-μm particle size, 150 × 4.60 mm diameter) column.…”

Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation

“…On the contrary, another acyclovir treatment formulated in PLGA nanoparticles employed vitamin E TPGS as a stabilising agent also displayed a biphasic release mechanism with rapid release followed by 72 h of controlled release [ 66 ]. In this study, the release rate followed the first-order release and obeyed Fick’s diffusion mechanism law instead.…”

“…The author explained that vitamin E TPGS contributed its inhibitory effect on the P-glycoprotein efflux transporter. On top of that, as mentioned in the Vadlapudi et al study, its self-assembly property improved acyclovir solubility via micellar formation to ultimately ameliorate the penetration process via inter- and intracellular pathways [ 59 , 66 , 67 ]. A hypothesis was made that pH affects the permeation of acyclovir, as both the pH level of the acyclovir solution and ACV-PLGA-TPGS nanoparticles shifted towards the neutral pH of the tear fluid.…”

“… Ocular irritation study conducted by Alkholief et al, revealing ( A ) normal condition of rabbit eye; ( B ) mild redness and inflammation in the conjunctival area by the first hour post-administration; ( C ) increased redness and inflammation by the third hour; ( D ) reduced redness and inflammation by the sixth hour; ( E ) complete reduction of redness and inflammation by the twelfth hour, adapted with permission from [ 66 ], Elsevier, 2019. …”