Potential Use of Polymeric Nanoparticles for Drug Delivery Across the Blood-Brain Barrier

Abstract

Nanomedicine is certainly one of the scientific and technological challenges of the coming years. In particular, biodegradable nanoparticles formulated from poly (D,L-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted delivery of different agents, including recombinant proteins, plasmid DNA, and low molecular weight compounds. PLGA NPs present some very attractive properties such as biodegradability and biocompatibility, protection of drug from degradation, possibility of sustained release, and the possibility to modify surface properties to target nanoparticles to specific organs or cells. Moreover, PLGA NPs have received the FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, thus reducing the time for human clinical applications. This review in particular deals on surface modification of PLGA NPs and their possibility of clinical applications, including treatment for brain pathologies such as brain tumors and Lysosomal Storage Disorders with neurological involvement. Since a great number of pharmacologically active molecules are not able to cross the Blood-Brain Barrier (BBB) and reach the Central Nervous System (CNS), new brain targeted polymeric PLGA NPs modified with glycopeptides (g7- NPs) have been recently produced. In this review several in vivo biodistribution studies and pharmacological proof-of evidence of brain delivery of model drugs are reported, demonstrating the ability of g7-NPs to create BBB interaction and trigger an efficacious BBB crossing. Moreover, another relevant development of NPs surface engineering was achieved by conjugating to the surface of g7-NPs, some specific and selective antibodies to drive NPs directly to a specific cell type once inside the CNS parenchyma.

Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment of intracranial glioma

“…IHC analysis of gH2A.X validates that the slowed tumor growth and significant increase in survival of animals treated with NP-20 was due to the enhanced tolerability of nanoparticle encapsulated CPT, which enabled a higher total dose to be delivered. PLGA is both biocompatible and biodegradable, and has been used extensively for improving the action of chemotherapeutics (Dawidczyk et al, 2014;Dinarvand et al, 2011;Gu et al, 2013;Guo et al, 2013;Tosi et al, 2013), including in humans. For example, PLA-PEG nanoparticles encapsulating the chemotherapeutic drug doxorubicin are the subject of a phase II clinical trial in prostate cancer and non-small cell lung carcinoma (Hrkach et al, 2012).…”

“…For example, poly (lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable polymer that can be formed into nanoparticles for encapsulation and sustained release of drug payloads. PLGA nanoparticles are capable of encapsulating a wide range of active agents for sustained release in biological environments, including CPT (Dawidczyk et al, 2014;Dinarvand et al, 2011;Tosi et al, 2013). CPT potency is improved by encapsulation and sustained release when infused directly into tumors (Cirpanli et al, 2010;Sawyer et al, 2011).…”

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

“…Indeed, NPs can be loaded with drugs or natural compounds showing enhanced intracranial drug delivery [18,19]. In particular, biodegradable and biocompatible NPs made with polylacticco-glycolic acid (PLGA) have been applied for the targeted delivery of different agents, including recombinant proteins, plasmid DNA, and low molecular weight compounds, such as phytochemicals [83]. Below, we summarize some examples on how NPs can be applied to improve phytocompound delivery to target GBM (Table 2).…”

PEG-g-Chitosan Nanoparticles Functionalized with the Monoclonal Antibody OX26 for Brain Drug Targeting

“…In order to increase the drug concentrations in the CNS, different approaches were attempted for the treatment of neurodegenerative diseases exploiting both invasive [7,8] or noninvasive methods. Noninvasive strategies for brain targeting include chemical modifications of the drugs (i.e., prodrugs), biochemical approaches (i.e., conjugation with specific antibodies) [9] or colloidal approach, based on nanomedicines, in particular, biodegradable PEG-g-chitosan nanoparticles functionalized with the monoclonal antibody OX26 for brain drug targeting Yuliana Monsalve 1 , Giovanni Tosi* ,2 , Barbara Ruozi 2 , Daniela Belletti 2 , Antonietta Vilella 3 , Michele Zoli 3 , Maria Angela Vandelli 2 , Flavio Forni 2 , Betty L López 1 & Ligia Sierra** ,1 1 polymeric nanoparticles (NPs) [10][11][12]. Advantages of this last strategy rely on the high chemical and biological stability of NPs, on the feasibility of incorporating both hydrophilic and hydrophobic pharmaceuticals by adsorption or encapsulation and on the possibility to administer the NPs by different routes (including noseto-brain, oral and parenteral) [1, [13][14].…”