Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration

Abstract

Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk

“…29,36 Moreover, in this study, we confirmed that LNC easily penetrates cell cytoplasm, indicating that intracellular pathways are the target of LNC or delivered drugs. Indeed, data presented in this study clearly show that LNC or AcE-LNC treatments improve the apoptosis of melanoma cells in different conditions associated with tumor microenvironment.…”

Nanomedicines for Cutaneous Leishmaniasis

“…The enhancing effect was possibly due to quercetin protection against extensive gastric and intestinal degradation [62]. Besides, PCL nanocapsules were shown to be absorbed intact by mouse intestinal epithelia [63] and also taken up by M cells [64]. Whether or not absorbed quercetin-loaded particles reach the circulation [65] and Leishmania-infected skin macrophages remained to be determined.…”

Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping

“…For example, rhodamine 6-labeled LNC drug shuttles were designed to deliver drugs across the BBB and into brain tissue with high efficiency, thus reducing glioblastoma after oral or intravenous administration. [22] Additionally, several notable examples of “nanomedicines” have been translated from bench to bedside, including liposomal Doxorubicin and Doxil. [93] Nanomedicine-based drugs in clinical trials or that have been clinically approved for the treatment of diseases related to the nervous system are shown in (Table 3).…”