Panoramic View of Biological Barricades and Their Influence on Polysaccharide Nanoparticle Transport: An Updated Status in Cancer

ABSTRACT

Biological barriers form a natural defensive barricade for the body, which screens the entry of foreign materials. Despite their protective role, they provide a major challenge for the transport of therapeutics across the biological barriers such as skin, oral, and intestinal mucosa, and blood- brain barrier. Pharmaceutical researchers are nowadays focusing on next-generation therapeutics based on larger biologicals (carrier-based systems). Polysaccharides, complex polymeric carbohydrates, have been studied far and wide as drug carrier systems in various forms. Polysaccharides belong to a class of drug carriers with advantageous properties such as nontoxic, biocompatible, biodegradable, and economic. The current review summarizes the studies reported on polysaccharide nanoparticles formulated for the transport across biological barricades with the aim of improving the anticancer potential.

The advanced research studies on the technological approaches for formulating and transporting a pharmaceutically active ingredient (or a drug) in the human body to achieve its desired therapeutic effect within the safety window have evolved through decades under the field of “drug delivery.” With the aim of improving patient convenience and compliance, various drug delivery systems (DDS) like controlled release systems were born in early 1950s (Park, 2016; Tiwari et al., 2012; Mirza and Siddiqui, 2014; NIH, 2016). The researchers working in the area of drug delivery in collaboration with dmg discoveiy have contributed immensely in developing new drug molecules as well as delivery systems toward almost all types of human diseases, where “cancer” is the main focus in this review. The World Health Organization (WHO) has listed cancer as one among the deadly and devastating diseases, which is characterized by the abnormal proliferation of cells with an invasive and metastatic potential (WHO, 2014, 2017). Irrespective of all of the therapeutic modalities developed against cancer, chemotherapy still remains to be the first line of treatment option.

Chemotherapy, the major cancer therapeutic strategy, involves the use of chemical molecules that act on fast-dividing cancer cells, thereby preventing their growth and killing them (Chabner and Roberts, 2005; Huang et al., 2017). The main class of anticancer diugs include alkylating agents (cispl- atin, procarbazine, cannustine, etc.), antimicrotubule agents (vinblastine, paclitaxel (PTX), etc.), antimetabolites (methotrexate, gemcitabine, etc.), topoisomerase inhibitors (etoposide, doxorubicin (DOX), etc.), and cytotoxic agents (bleomycin) (Cirenajwis et al., 2010). Anticancer diugs are generally administered orally in the form of pills or via different parenteral routes such as intramuscular, intravenous (IV), intraperitoneal, or subcutaneous in the form of injectable formulations or infusions. Diugs administered orally go through absorption steps and hence circulate for longer time in the body. Also considering patient convenience, oral fonnulations are preferred. However, in general, chemotherapies prefer parenteral injections or infusions since they bypass first pass metabolism as the diugs are directly given to the blood stream for its accelerated action. However, irrespective of these routes of administrations, the diug molecule has to pass through different biological barriers.

The organisms evolved by creating certain biological banders on their own, which was differentiated upon the requirement to regulate water content, homeostasis, gas exchange, nutritional availability, waste excretion, and the protective role indeed. The functions were managed by the development of tissues for specific requirements such as skin for environment sensing

(water and homeostasis regulation), lungs for oxygen exchange, intestine for nutrient passage, etc. The aforementioned play the role of structural barriers for drag delivery, and hence, DDS developers focus on the specific interaction of the developed systems with these tissues and finally deliver the cargo to the desired target site. The preliminary consideration would be on the main biological barriers such as skin, oral and nasal mucosa, gastrointestinal (GI) tract, and blood-brain barrier (BBB). Cancer represents the best example of a disease condition where the adequacy of delivering chemotherapeutics with highly potent, yet toxic, mechanisms of action means the difference between efficacious responses and severe morbidity. Pharmaceutical industries started utilizing larger biological “carrier-bound drugs” as next-generation cancer chemotherapeutics, where nanocarriers opened up new opportunities. These nanoplatforms have been materialized as suitable vectors for overcoming pharmacokinetic limitations associated with conventional drug formulations. Many of these nanoplatforms improved patient safety and morbidity, which led to their clinical approval. However, these platforms offer only marginal improvements over conventional formulations. The complex series of biological barricades reduce the site-specific bioavailability of the therapeutic agent from these platforms and thereby prevent achieving proper therapeutic outcomes, resulting in undesired toxicological profiles. Here comes the need for nontoxic biocompatible materials for developing drug carriers, where natural polysaccharides are gaining great interests.

This monograph attempted to give a brief update on biocompatible polysaccharide-based nano-DDS for the administration of anticancer drugs through different routes, highlighting the potential to cross various biological barricades and reach the diseased target site and eliciting their anticancer therapeutic potentials.