In vivo characterization of a polymeric nanoparticle platform with potential oral drug delivery capabilities

Abstract

Nanotechnology has enabled significant advances in the areas of cancer diagnosis and therapy. The field of drug delivery is a sterling example, with nanoparticles being increasingly used for generating therapeutic formulations of poorly water-soluble, yet potent anticancer drugs. Whereas a number of nanoparticle-drug combinations are at various stages of preclinical or clinical assessment, the overwhelming majorities of such systems are injectable formulations and are incapable of being partaken orally. The development of an oral nano-delivery system would have distinct advantages for cancer chemotherapy. We report the synthesis and physicochemical characterization of orally bioavailable polymeric nanoparticles composed of N-isopropylacrylamide, methylmethacrylate, and acrylic acid in the molar ratios of 60:20:20 (designated NMA622). Amphiphilic NMA622 nanoparticles show a size distribution of <100 nm (mean diameter of 80 ± 34 nm) with low polydispersity and can readily encapsulate a number of poorly water-soluble drugs such as rapamycin within the hydrophobic core. No apparent systemic toxicities are observed in mice receiving as much as 500 mg/kg of the orally administered void NMA622 for 4 weeks. Using NMA622-encapsulated rapamycin (“nanorapamycin”) as a prototype for oral nano-drug delivery, we show favorable in vivo pharmacokinetics and therapeutic efficacy in a xenograft model of human pancreatic cancer. Oral nanorapamycin leads to robust inhibition of the mammalian target of rapamycin pathway in pancreatic cancer xenografts, which is accompanied by significant growth inhibition (P < 0.01) compared with control tumors. These data indicate that NMA622 nanoparticles provide a suitable platform for oral delivery of water-insoluble drugs like rapamycin for cancer therapy.

Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer

“…Though a number of nanoparticle-drug combinations are assessed in preclinical or clinical applications, most of delivery systems are intravenously injectable formulations and are incapable of oral administration [17,18]. On the other hand, it has been reported that nanocomposites such as silver nanoparticle for therapeutics itself exhibits the undesired toxicity on the GI tract after repeated oral administration [19,20].…”

Nanoparticles: A Promising Drug Delivery Approach

“…It was reviewed that polymeric nanoparticles prevent inactivation and degradation caused by acidic pH and digestive enzymes [57]. A nanoparticle adheres to the mucosa and thus enhances the absorption of the associated drug [63]. Neonatal Fc receptor present in the small intestine and colon is the target for nanoparticles [64].…”

Aplicações farmacêuticas de polímeros

“…Os primeiros medicamentos injetáveis comercializados na forma de microesferas foram o Parlodel ® LAR e o Sandostatin ® LAR (laboratório Sandoz), ambos baseados em matrizes de PLGA [122] . As nanopartículas poliméricas -nanocápsulas e nanoesferas -são sistemas que apresentam aplicações promissoras, principalmente, na vetorização de anticancerígenos, proteínas, peptídeos, vacinas tumorais e material para terapia gênica administrados pela via parenteral e, também, administração de antibióticos pela via oral [123][124][125][126] . Os principais polímeros empregados na preparação de nanocarreadores são os naturais modificados, derivados da albumina, colágeno, ácido hialurônico, gelatina, quitosana e alginato, além dos polímeros sintéticos PHEMA, PVA, PAA, PEVA, PEG e a poli(acrilamida).…”