Oral peptide delivery using nanoparticles composed of novel graft copolymers having hydrophobic backbone and hydrophilic branches

Sakuma, Shinji; Suzuki, Norio; Kikuchi, Hiroshi; Hiwatari, Ken‐ichiro; Arikawa, Kiyotaka; Kishida, Akio; Akashi, Mitsuru

doi:10.1016/s0378-5173(96)04861-2

Cited by 84 publications

(51 citation statements)

References 42 publications

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“…9,10 After oral administration, the nanoparticles could control the release of drugs, reduce gastrointestinal mucosal irritation, and ensure their stability in the gastrointestinal tract. 11 Lecithin nanoparticles (LNs) were reported to be able to increase antitumor effects of docetaxel after intravenous injection with good biocompatibility. 12 Lecithin is a combination of acetone-insoluble phosphatides that combines with various amounts of other substances such as triglycerides and fatty acids.…”

Section: Introductionmentioning

confidence: 99%

Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation

Cao²,

Hu³

et al. 2012

IJN

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Abstract:The aim of this research work was to investigate the potential of lecithin nanoparticles (LNs) in improving the oral bioavailability of docetaxel. Docetaxel-loaded LNs (DTXLNs) were prepared from oil-in-water emulsions and characterized in terms of morphology, size, zeta potential, and encapsulation efficiency. The in vitro release of docetaxel from the nanoparticles was studied by using dialysis bag method. Caco-2 cell monolayer was used for the in vitro permeation study of DTX-LNs. Bioavailability studies were conducted in rats and different pharmacokinetic parameters were evaluated after oral administration of DTX-LNs. The results showed that DTX-LNs had a mean diameter of 360 ± 8 nm and exhibited spherical shape with smooth surface under transmission electron microscopy. The DTX-LNs showed a sustained-release profile, with about 80% of docetaxel released within 72 hours. The apical to basolateral transport of docetaxel across the Caco-2 cell monolayer from the DTX-LNs was 2.14 times compared to that of the docetaxel solution (0.15 × 10 −5 ± 0.016 × 10 −5 cm/second versus 0.07 × 10 −5 ± 0.003 × 10 −5 cm/second). The oral bioavailability of the DTX-LNs was 3.65 times that of docetaxel solution (8.75% versus 2.40%). These results indicate that DTX-LNs were valuable as an oral drug delivery system to enhance the absorption of docetaxel.

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Section: Introductionmentioning

confidence: 99%

Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation

Cao²,

Hu³

et al. 2012

IJN

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“…Existem vários métodos relatados na literatura para a preparação de nanopartículas poliméricas, os quais podem ser, de uma forma geral, classificados em métodos baseados na polimerização in situ de monômeros dispersos (cianoacrilato de alquila) [24][25][26][27][28] ou na precipitação de polímeros pré-formados 11,[29][30][31][32][33] , tais como poli(ácido lático) (PLA), poli(ácido lático-co-ácido glicólico) (PLGA), poli(ε-caprolactona) (PCL) e, ainda, os copolímeros do ácido metacrílico e de um éster acrílico ou metacrílico. A Figura 2 apresenta as principais etapas dos diferentes métodos de preparação de nanopartículas [34][35][36] .…”

Section: Introductionunclassified

Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos

et al. 2003

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Recebido em 28/10/02; aceito em 27/2/03 PHYSICOCHEMICAL CHARACTERIZATION AND STABILITY OF THE POLYMERIC NANOPARTICLE SYSTEMS FOR DRUG ADMINISTRATION. Polymeric nanoparticle systems such as nanocapsules and nanospheres present potential applications for the administration of therapeutic molecules. The physico-chemical characteristics of nanoparticle suspensions are important pre-requisites of the success of any dosage form development. The purpose of this review is to present the state of the art regarding the physico-chemical characterization of these drug carriers, in terms of the particle size distribution, the morphology, the polymer molecular weight, the surface charge, the drug content and the in vitro drug release profiles. Part of the review is devoted to the description of the techniques to improve the stability of colloidal systems.Keywords: nanoparticles; polymers; characterization. INTRODUÇÃOO controle da liberação de fármacos em sítios de ação específi-cos, através da utilização de vetores, capazes de permitir a otimização da velocidade de cedência e do regime de dosagem das substâncias, tem sido uma área de intensa pesquisa nos últimos dez anos. Dentre os vetores, incluem-se as micropartículas e os sistemas coloidais (lipossomas e nanopartículas). As nanopartículas, constituídas por polímeros biodegradáveis, têm atraído maior atenção dos pesquisadores em relação aos lipossomas, devido às suas potencialidades terapêuticas, à maior estabilidade nos fluídos biológicos e durante o armazenamento 1-3 . As nanopartículas poliméricas são sistemas carreadores de fármacos que apresentam diâmetro inferior a 1 µm. O termo nanopartícula inclui as nanocápsulas e as nanoesferas, as quais diferem entre si segundo a composição e organização estrutural (Figura 1). As nanocápsulas são constituídas por um invólucro polimérico disposto ao redor de um núcleo oleoso, podendo o fármaco estar dissolvido neste núcleo e/ou adsorvido à parede polimérica. Por outro lado, as nanoesferas, que não apresentam óleo em sua composição, são formadas por uma matriz polimérica, onde o fármaco pode ficar retido ou adsorvido 2,4,5 . Estes sistemas têm sido desenvolvidos visando inúmeras aplicações terapêuticas, sendo planejados, principalmente, para administração parenteral, oral ou oftálmica. Uma das áreas mais promissoras na utilização das nanopartículas é a vetorização de fármacos anticancerígenos 2,6-8 e de antibióticos 2,9,10 , principalmente através de administração parenteral, almejando uma distribuição mais seletiva dos mesmos e, assim, um aumento do índice terapêutico. Com relação à administração oral de nanopartículas, as pesquisas têm sido direcionadas especialmente à: a) diminuição dos efeitos colaterais de certos fármacos, destacando-se os antiinflamatórios não-esteróides (diclofenaco 11,12 , indometacina 13-15 ), os quais causam freqüentemente irritação à mucosa gastrintestinal e b) proteção de fármacos degradáveis no trato gastrintestinal, como peptídeos 16,17 , proteínas 8,18 e/ou hormônios 19 , aumentando a biodisponi...

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“…40) Our data (F, 0.43%) indicated that the mucoadhesive W/O/W emulsion containing EC gave relatively higher F value compared with those (the estimated values from the AUCs) reported by others. 17,18,40,41) EC could thus be delivered slightly but effectively in the biologically active form through the intestinal epithelium, offering the possibility of its oral delivery.…”

Section: Discussionmentioning

confidence: 99%

Oral Delivery of Synthetic Eel Calcitonin, Elcatonin, in Rats.

Ogiso

Funahashi

Tsukioka

et al. 2001

Biological & Pharmaceutical Bulletin

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Recent advances in biotechnology have made available large numbers of bioactive peptides, which may have therapeutic potential. Many polypeptides are susceptible to degradation by proteolytic enzymes and are poorly absorbed in the gastrointestinal tract. With very few exceptions of small and cyclic peptides such as cyclosporin, most peptide drugs have low oral bioavailabilities with typical values of less than 1%. 1)There are many examples of the use of particulate systems which attempt to achieve systemic delivery of peptide drugs via the intestinal tract. These include nanoparticles, 2-5) microspheres, 2,6) liposomes 7,8) and multiple emulsions 9,10) that shield peptide drugs from enzymatic attack.Elcatonin (EC), synthetic [Asu 1,7 ]-eel calcitonin and a hypocalcemic peptide, has been used for the treatment of Paget's disease as well as certain types of osteoporosis. 11)The usual routes of its administration are subcutaneous and intramuscular. On the other hand, intranasal administration of human calcitonin (hCT) and salmon calcitonin (sCT) has proved effective in the management of Paget's disease 12,13) and postmenopausal osteoporosis.14-16) The colonic absorption of 125 I-hCT in humans 17) and the rectal absorption of EC in rabbits 18) have been recently evaluated, estimating the hypocalcemic effect. However, among all alternative routes for administration of EC and calcitonin, the oral route is a suitable alternative, because it offers improved convenience and patient compliance. It is of particular interest that EC has considerable resistance to enzymatic degradation conformationally, 19) a property which is beneficial to the oral administration. In order to meet these challenges we aimed to develop an oral dosage form whose EC bioavailability would be sufficient to promote the hypocalcemic response at the same level as obtained with parental dosage forms.This paper describes an approach to oral administration of EC in rats. We have estimated the intestinal absorption of EC coadministered with some protease inhibitors and absorption enhancers. In addition, to realize the oral delivery of EC, mucoadhesive W/O/W multiple emulsions and a capsule of the peptide were prepared and the hypocalcemic effects were evaluated in rats after their oral administration. We discuss the possibility of oral delivery of EC for the treatment of disease based on the results obtained. Treatment of Animals Male Wistar rats (Japan SLC, Shizuoka, Japan), weighing 200-240 g, were used throughout this experiment. The animals were maintained on MF diet (Oriental Yeast Co., Tokyo) for 3-4 d prior to the experiment. A group of 3-7 rats was randomly selected from the population. On the day before the experiment, the rat jugular vein was cannulated with silicon tubing, 20) and the rat was fasted overnight (for 16 h). MATERIALS AND METHODS Materials Preparation of W/O/W Multiple Emulsions and Mucoadhesive EmulsionsThe multiple emulsions were prepared by a two-step process.21) The primary emulsion con- * To whom correspondence should be add...

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Oral peptide delivery using nanoparticles composed of novel graft copolymers having hydrophobic backbone and hydrophilic branches

Cited by 84 publications

References 42 publications

Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation

Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation

Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos

Oral Delivery of Synthetic Eel Calcitonin, Elcatonin, in Rats.

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