Nanoparticle Formulation Increases Oral Bioavailability of Poorly Soluble Drugs: Approaches, Experimental Evidences and Theory

Abstract

The increasing frequency at which poorly soluble new chemical entities are being discovered raises concerns in the pharmaceutical industry about drugability associated with erratic dissolution and low bioavailability of these hydrophobic compounds. Nanonization provides a plausible pharmaceutical basis for enhancing oral bioavailability and therapeutic effectiveness of these compounds by increasing their surface area. This paper surveys methods available to pharmaceutical manufacturing nanoparticles, including wet chemical processes, media milling, high pressure homogenization, gasphase synthesis, and form-in-place processes, and elaborates physicochemical rational and gastrointestinal physiological basis upon which nano-drugs can be readily absorbed. Relevant examples are illustrated to show that nano-drugs permeate Caco-2 cell monolayer fast and are well absorbed into animal systemic circulation with high T max and AUC, resulting in oral bioavailability higher than their counterpart micro-drugs. The size-dependent permeability and bioavailability should be given particular consideration in the development of potent and selective drug candidates with poor aqueous solubility.

Possible Synergistic Effect and Antioxidant Properties of Chitosan Nanoparticles and Quercetin against Carbon Tetrachloride-Induce Hepatotoxicity in Rats

“…As a solution for the water-insolubility problem of chitosan, nanoparticle formulation provides a plausible pharmaceutical basis for enhancing oral bioavailability and therapeutic efficacy of chitosan and other drugs that are poorly soluble [26]. In addition, nanoparticles possess a stronger curvature of the surface, compared to large particles; this produces more dissolution pressure with a corresponding increase in saturation solubility [27].…”

“…However, because of its high molecular weight and water-insolubility, the applications of chitosan are severely limited. As a solution, nanoparticle formulation provides a plausible pharmaceutical basis for enhancing oral bioavailability and therapeutic efficacy of chitosan and other drugs that are poorly soluble [26]. Chitosan nanoparticles (CNPs) exhibit more superior activities than chitosan and have been reported to have heightened immune-enhancing effect, anticancer activity and antimicrobial activity than those of chitosan.…”

Nanotechnology towards prevention of anaemia and osteoporosis: from concept to market

“…Min et al [5] reported that the drug stability and tumour-targeting ability of camptothecin, encapsulated in glycol chitosan nanoparticles that have been hydrophically modified by conjugating 5b-cholanic acid moieties, were higher than those of free camptothecin, as observed in mice models. Lee Jia [6] reported that nanonization of two poorly soluble drugs, carbenzandim and thiadiazole derivative, increases their oral bioavailability both in in vivo (SCID mice and Sprague-Dawley rats)and in vitro (Caco-2 cell lines) models. When the drugs were reduced to a size of 280 nm by pearl milling, their bioavailability was much higher than that of the micro-sized counterparts [6].…”

“…Lee Jia [6] reported that nanonization of two poorly soluble drugs, carbenzandim and thiadiazole derivative, increases their oral bioavailability both in in vivo (SCID mice and Sprague-Dawley rats)and in vitro (Caco-2 cell lines) models. When the drugs were reduced to a size of 280 nm by pearl milling, their bioavailability was much higher than that of the micro-sized counterparts [6]. Mahler et al [7] showed that oral exposure to polystyrene nanoparticles affected iron uptake and absorption through in vivo studies in chickens and in vitro studies in Caco-2 and HT29/MTX cell lines.…”

Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

“…Carbon lattices, metal oxides, micelles, liposomes, nanotubes and polymers, and many more examples of nanomaterials are made of diameter of less than 100 nm (0.1μm). Particle aggregates are capable of being broken down to even smaller particles through milling and/or dispersion which generates nanoscale particles rather than solvated materials [13]. The relatively increased surface area, the quantum effects (in some cases), and the nano-scale size are the three principal factors that give nanomaterials their distinct properties that distinguish them from the bulk materials.…”