Pharmacokinetic Aspects of Nanoparticle-in-Matrix Drug Delivery Systems for Oral/Buccal Delivery

Abstract

Oral route maintains its predominance among the ones used for drug delivery, especially when medicines are self-administered. If the dosage form is solid, therapy gains in dose precision and drug stability. Yet, some active pharmaceutical substances do not present the required solubility, permeability, or release profile for incorporation into traditional matrices. The combination of nanostructured drugs (nanoparticle [NP]) with these matrices is a new and little-explored alternative, which could bring several benefits. Therefore, this review focused on combined delivery systems based on nanostructures to administer drugs by the oral cavity, intended for buccal, sublingual, gastric, or intestinal absorption. We analyzed published NP-in-matrix systems and compared main formulation characteristics, pharmacokinetics, release profiles, and physicochemical stability improvements. The reported formulations are mainly semisolid or solid polymers, with polymeric or lipid NPs and one active pharmaceutical ingredient. Regarding drug specifics, most of them are poorly permeable or greatly metabolized. The few studies with pharmacokinetics showed increased drug bioavailability and, sometimes, a controlled release rate. From our knowledge, the gathered data make up the first focused review of these trendy systems, which we believe will help to gain scientific deepness and future advancements in the field.

Keywords: buccal delivery; drug absorption; matrix delivery; nanoparticle; oral delivery.

Figure 1

Scheme (not to scale) of drug (blue circles) loaded nanoparticles (NPs, yellow circles) interacting with physiological environments. Nanoparticle modes to enhance drug systemic delivery through the oral or buccal routes. 1: Lumen release (solubility enhancement), followed by NP excretion or degradation. 2: Adherence to mucus or mucosal surface for enhanced drug absorption (no NP permeation), followed by NP excretion or degradation. 3: NP absorption for enhanced plasma half-life, followed by NP liver degradation or lymphatic drainage. 4: Tissue or cell targeting. Figure created for this review in CorelDRAW Graphics Suite X7.

Figure 2

Scheme (not to scale) of the failure modes of nanoparticles (NPs, yellow circles) loaded with drug (blue circles) after oral/buccal administration: early washout in mouth or intestinal cavities; early degradation due to pH or enzymes; burst release upon contact with aqueous media (saliva, stomach acid); aggregation due to pH, osmotic environment, and protein binding. The network on the left shows matrix protection through adhesion (wash out elimination), shielding (degradation and burst elimination/decrease), and physical separation (aggregation elimination). Figure created for this review in CorelDRAW Graphics Suite X7 and Adobe Photoshop CS6.