Polymer-based nanoparticles for oral insulin delivery: Revisited approaches.
Diabetes mellitus is a high prevalence and one of the most severe and lethal diseases in the world. Insulin is commonly used to treat diabetes in order to give patients a better life condition. However, due to bioavailability problems, the most common route of insulin administration is the subcutaneous route, which may present patients compliance problems to treatment. The oral administration is thus considered the most convenient alternative to deliver insulin, but it faces important challenges. The low stability of insulin in the gastrointestinal tract and low intestinal permeation, are problems to overcome. Therefore, the encapsulation of insulin into polymer-based nanoparticles is presented as a good strategy to improve insulin oral bioavailability. In the last years, different strategies and polymers have been used to encapsulate insulin and deliver it orally. Polymers with distinct properties from natural or synthetic sources have been used to achieve this aim, and among them may be found chitosan, dextran, alginate, poly(γ-glutamic acid), hyaluronic acid, poly(lactic acid), poly(lactide-co-glycolic acid), polycaprolactone (PCL), acrylic polymers and polyallylamine. Promising studies have been developed and positive results were obtained, but there is not a polymeric-based nanoparticle system to deliver insulin orally available in the market yet. There is also a lack of long term toxicity studies about the safety of the developed carriers. Thus, the aims of this review are first to provide a deep understanding on the oral delivery of insulin and the possible routes for its uptake, and then to overview the evolution of this field in the last years of research of insulin-loaded polymer-based nanoparticles in the academic and industrial fields. Toxicity concerns of the discussed nanocarriers are also addressed.
REQUINTE, Department of Chemical Sciences-Applied Chemistry Lab, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal.
Pedro
P
Fonte
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal; ICBAS-Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; INEB-Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland.
Francisca
F
Araújo
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal.
Cátia
C
Silva
INEB-Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Carla
C
Pereira
REQUINTE, Department of Chemical Sciences-Applied Chemistry Lab, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Salette
S
Reis
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014 University of Helsinki, Finland.
Hélder A
HA
Santos
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal; INEB-Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
Bruno
B
Sarmento
D000284:Administration, Oral; D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
D000464:Alginates; D003911:Dextrans; D004337:Drug Carriers; D007328:Insulin; D011073:Polyamines; D011091:Polyesters; D011108:Polymers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; C063994:polyallylamine; D019344:Lactic Acid; C033616:poly(lactide); D006820:Hyaluronic Acid; D048271:Chitosan
Chitosan; Diabetes; Insulin; Intestinal uptake; Oral delivery; Poly(lactic-co-glycolic acid); Polymeric nanoparticles