Nanotechnology-Based Biopolymeric Oral Delivery Platforms for Advanced Cancer Treatment

Abstract

Routes of drug administration and their corresponding physiochemical characteristics play major roles in drug therapeutic efficiency and biological effects. Each route of delivery has favourable aspects and limitations. The oral route of delivery is the most convenient, widely accepted and safe route. However, the oral route of chemotherapeutics to date have displayed high gastric degradation, low aqueous solubility, poor formulation stability and minimum intestinal absorption. Thus, mainstream anti-cancer drugs in current formulations are not suitable as oral chemotherapeutic formulations. The use of biopolymers such as chitosan, gelatin, hyaluronic acid and polyglutamic acid, for the synthesis of oral delivery platforms, have potential to help overcome problems associated with oral delivery of chemotherapeutics. Biopolymers have favourable stimuli-responsive properties, and thus can be used to improve oral bioavailability of anti-cancer drugs. These biopolymeric formulations can protect gastric-sensitive drugs from pH degradation, target specific binding sites for targeted absorption and consequently control drug release. In this review, the use of various biopolymers as oral drug delivery systems for chemotherapeutics will be discussed.

Keywords: biopolymers; cancer; cancer nanotechnology; nanoparticles; oral delivery; targeted drug delivery.

Figure 1

Schematic representation of crosslinking methods used to formulate gelatin nano-materials. Adapted and modified with permission from [14].

Figure 2

Example of a formulation method for the preparation of poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs). Diagram shows preparation of PLGA NPs for the simultaneous delivery of two different drugs. The drug-loaded NPs are prepared by a double emulsion-solvent evaporation method. Abbreviations: PVA—polyvinyl alcohol; EA—ethyl acetate. Adapted and modified with permission from [31].

Figure 3

Schematic illustration of the three ways of complexation or conjugation of anti-cancer drugs with a dendrimer molecule. (A) Encapsulation of the chemotherapeutic into the internal cavity, (B) surface conjugation of chemotherapeutic onto the peripheral of the dendrimer molecule, and (C) same dendritic molecule can serve a carrier for both encapsulated and surface-conjugated anti-cancer drugs. Adapted and modified with permission from [71].

Figure 4

(A) Photo-sensitive liposomal assembly. Drugs (red), imaging agents and/or second photosensitizer (bright blue) are encapsulated in the liposomes. (B) Chemical structure shown as a prototype. The three lipid parts—that is, the head, glycerol backbone and fatty acyl chains—can be modified to generate photo-sensitive materials. Adapted and modified with permission from [81].

Figure 5

Schematic representation of a surface modified nanoparticle, highlighting examples of ligands used in surface modification and attachment to receptor site. Adapted and modified with permission from [89].

Figure 6

Schematic illustration of an example of self-assembled pH-responsive doxorubicin loaded micelles. The micelles were formulated using hydrophilic PEG and hydrophobic pH-sensitive PAE. The micelles will remain stable at normal sites (pH = 7.4), only to respond at the targeted site with the desired pH (pH < 6.5). Abbreviations: PEG—poly(ethylene glycol), PAE—poly(β-amino esters) g-cholesterol, and DOX—doxorubicin. Adapted and modified with permission from [92].