New Peptide Functionalized Nanostructured Lipid Carriers with CNS Drugs and Evaluation Anti-proliferative Activity

Abstract

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper. In this paper, we described the synthesis of a new conjugated of tranylcypromine with MAP. In addition, taking into consideration our previous results, this study developed different NLCs loaded with three central nervous system (CNS) drugs (tacrine (TAC), rasagiline (RAS), and tranylcypromine (TCP)) functionalized with model amphipathic peptide (MAP) and evaluated their activity against cancer cells. Particle size analysis demonstrated NLC presented less than 200 nm and a polydispersity index less than 0.3. Moreover, in vitro results showed that conjugation of MAP with drugs led to a higher decrease in cell viability of a neuroblastoma cell line and Caco-2 cell line, more than MAP alone. Furthermore, NLC encapsulation contributed to higher cellular delivery and enhanced toxic activity at lower concentrations when compared with free or co-administration drug-MAP conjugate.

Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders

“…Functionalized nanoparticles offer advantages in prolonging the residence time of therapeutic agents at the BBB and enhancing their penetration [9,[20][21][22][23]. Moreover, brain delivery can be achieved using lipid nanocarriers for active targeting [64][65][66][67][68][69][70]. Active targeting consists of attaching ligands to the surface of the nanosystem or CPPs [10,12] in order to promote interaction with proteins constitutively expressed at the BBB, such as the low-density lipoprotein receptor [71,72], transferrin (Tfr) [73], and insulin receptor [49,50,74].…”

“…Cubosomes are lipidic nanoparticles with an internal cubic structure of bicontinuous cubic or micellar cubic types. They can be formed by the self-assembly of lipid mixtures involving nonlamellar lipids [57,66]. The bicontinuous lipid cubic phase encompasses a lipid bilayer with a periodic minimal surface intertwined with a three-dimensional network of water nanochannels.…”

A Second Life for MAP, a Model Amphipathic Peptide

“…The authors observed a decrease of 50% cell viability at a concentration of 2.5 µM for SH-SY5Y and 5 µM for MCF-7, and with loss of morphological appearance and high cell death at 20 µM [ 66 ]. The same authors further observed an increase in the antiproliferative effect of MAPs conjugated with the central nervous system (tranylcypromine and rasagiline) against neuroblastoma cell line SH-SY5Y and colorectal adenocarcinoma Caco-2 cell lines when compared to MAPs alone and a MAP derivate (Lys(N 3 )-MAP) [ 67 ]. In a different work, the toxic activity was also observed by Moutal et al, with treatment of MAPs conjugated with Ca 2+ channel binding domain 3 (CBD3) on cortical neuron cultures.…”

“…In the following work, the authors evaluated two more conjugates, tranylcypromine-MAP and rasagiline-MAP, encapsulated into the same lipid nanoparticles in vitro. The results demonstrated that incorporation of both conjugates into nanoparticles led to a significant decrease in cell viability at lower concentrations on both cell line studies (SH-SY5Y and Caco-2) when compared to the conjugates administered alone [ 67 ]. These results demonstrated the potential use of this strategy in new therapeutic approaches, reducing the amount of drug use and increasing the therapeutic efficacy.…”