Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier

Abstract

Background P-glycoprotein (P-gp) mediated drug efflux across the blood–brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG). Methods LTG-loaded Pluronic ® P123 (P123) polymeric micelles (P123/LTG) were prepared by thin-film hydration, and brain penetration capability of the nanocarrier was evaluated. Results The mean encapsulating efficiency for the optimized formulation was 98.07%; drug-loading was 5.63%, and particle size was 18.73 nm. The solubility of LTG in P123/LTG can increase to 2.17 mg/mL, making it available as a solution. The in vitro release of LTG from P123LTG presented a sustained-release property. Compared with free LTG, the LTG-incorporated micelles accumulated more in the brain at 0.5, 1, and 4 hours after intravenous administration in rats. Pretreatment with systemic verapamil increased the rapid brain penetration of free LTG but not P123/LTG. Incorporating another P-gp substrate (Rhodamine 123) into P123 micelles also showed higher efficiency in penetrating the BBB in vitro and in vivo. Conclusion These results indicated that P123 micelles have the potential to overcome the activity of P-gp expressed on the BBB and therefore show potential for the targeted delivery of AEDs. Future studies are necessary to further evaluate the appropriateness of the nanocarrier to enhance the efficacy of AEDs.

Pluronic P123 modified nano micelles loaded with doxorubicin enhanced tumor-suppressing effect on drug-resistant breast cancer cells

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Pluronics-Formulated Farnesol Promotes Efficient Killing and Demonstrates Novel Interactions with Streptococcus mutans Biofilms

“…Pluronic copolymers are FDA-approved and have been used to efficiently formulate various drugs for their delivery to the stomach [ 39 ], brain [ 40 , 41 ], liver [ 42 ], and various tumor cells [ 43 – 47 ]. Additionally, Pluronics conjugated to alendronate, pyrophosphate, and phosphoserine have shown great promise as tooth-targeting systems when used in the micellar formulation of hydrophobic antimicrobial compounds [ 26 – 28 ].…”

Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders

“…Direct delivery of drugs into the brain by intracerebral or intracerebroventricular routes are considered important approaches for the management of epilepsy, especially in drug-resistant patients [ 86 ]. Several studies have used nanoformulations for the targeted delivery of antiepileptic drugs to the receptor site via intravenous, oral, intranasal, and transdermal routes [ 87 , 88 ]. Only a few reports can also be found on the NE-based direct nose-to-brain delivery of antiepileptic drugs.…”