POLYSACCHARIDE NANOPARTICLES CROSSING THE BLOOD-BRAIN BARRIER
Polysaccharide-based colloidal drug carriers in the form of emulsions, micelles, liposomes dendrimers, and NPs were developed as nanomedicines, which provide a potential platform to be developed as therapeutic strategies to pass through BBB. However, only a few investigations have been done in the case of polysaccharide anticancer strategies against BBB. Plenty of CS-based transport systems have been reported for overcoming BBB. (3-cyclodextrin (p-CD) is a potential polysaccharide studied for BBB crossing. Aktas et al. (2005) synthesized transferrin receptor (TfR)-targeted CS nanospheres conjugated with poly(ethylene glycol) (PEG) bearing the 0X26 monoclonal antibody that triggered receptor-mediated transport across the BBB. They designed these NPs for the delivery of the caspase inhibitor peptide, and the systemically administered systems were found to provide significant concentration of the peptide in the brain tissues. The electrostatic interaction between these cationic particles and the negatively charged brain endothelium could be responsible for the targeted-induced transport across the BBB (Aktas et al., 2005). p-CD was modified using poly(p-amino ester) and formulated into nanogels coloaded with DOX and insulin. The hydrophobic cavity provided space for hydrophobic drugs and the outer polysaccharide layer gives opportunity for loading hydrophilic moieties and showed enhanced permeability over blood-brain microendothelial cells. The same group prepared NPs with the same material and found that they had higher permeability across in vitro BBB models (Gil et al., 2012). Hydroxypropyl-b-cyclodextrin enhanced the solubility of puerarin and gelatin, which in turn improved the viscosity of theinner water phase, resulting in enhanced entrapment of puerarin. It was also proposed that nanocarriers or cyclodextrin inclusion complex enhanced the penetration of drug across the BBB (Tao et al., 2013).
POLYSACCHARIDE NANOPARTICLES CROSSING OTHER BARRIERS
In addition to the above-discussed barriers, drug delivery candidates were exposed to nasal mucosa, rectal mucosa, and vaginal and ophthalmic barriers. However, not many researchers have exploited these routes for delivering therapeutic agents for cancer treatment.
Nasal mucosa forms a barrier for delivering therapeutic agents to lungs as well as to brain. Nasal administrations of drugs provide an alternative administration route for brain disorders, where BBB forms the main challenging barricade. Mucoadhesive polymer CS was reported to be beneficial in binding to nasal mucosa and improving the drug concentration in the lungs as well as CS aerosols directly reaching brain from the nose bypassing BBB (Kaur et al., 2012). Majority of the studies focused on the use of CS NPs for the nasal delivery of proteins, peptides, or nucleic acids as antigens, vaccines, or genetherapy (Kaur et al., 2012; van Woensel et al., 2013). DNA vaccine loaded into mannosylated chitosan (MCS) NPs was intranasally administered to prostate cancer (subcutaneous)-bearing mice by Yao et al. (2013). They reported that these MCS targeted antigen-presenting cells, enhanced mannose-mediated cancer cell uptake, and enhanced the intranasal administration, resulting in high level of anti-GRP antibody and thereby inhibiting tumor growth. Thus, MCS offered efficient tumor immunotherapy (Yao et al., 2013). PTX-loaded alginate microparticles have been developed for site-specific pulmonary delivery of drugs to mucosal tissues. Results show that the exposure of cells to pure PTX and PTX-loaded microparticles effectively inhibited the growth of A549 and Calu-6 cells, similarly in concentration- and time-dependent manners (Alipour et al., 2010). Similarly HA, carboxymethyl cellulose, and cyclodextrins have been reported to be studied for nasal drug delivery (Kaur et al., 2012). Feng et al. reported DOX-loaded CS and CMC nanogels with high mucin binding and inhibiting paracellular transpoit to the colon. This enhanced mucoadhesion and limited permeability prolonged the contact tune with the intestinal mucosa, resulting in local drug concentration. These nanogels can be further exploited for local colorectal cancer therapy (Feng et al., 2015). In 2012, Pandekal et al. developed a CS-polycarbophil interpolyelectrolyte (IPEC) complex, which was later compressed with tablets of anticancer drug 5-FU. This 5FU-IPEC was evaluated for drag release at different pH values simulating buccal cavity, vagina, and rectum. The formulations showed controlled release of 5-FU with the highest bioadhesive property and satisfactoiy residence in both buccal and vaginal cavities of rabbit. Formulation with 3% of sodium deoxycholate exhibited maximum permeation of 5-FU. The study thus proved that a suitable combination of IPEC, CS, and polycarbophil demonstrated a potential candidate for controlled release of 5-FU in buccal, vaginal, and rectal pH (Pendekal and Tegginamat, 2012).
Extensive research is needed where biocompatible natural polysaccharides can be utilized to form cancer nanomedicines to exploit other nonin- vasive administration routes so that lives of cancer patients can be saved worldwide.