Hirofumi Takeuchi,Kohei Tahara,Risako Onodera

Gifu Pharmaceutical University,1-25-4 Daigaku-nishi,Gifu 501-1196,Japan

Recent advances in particulate drug delivery systems:Oral,pulmonary,and ophthalmic administrations

Hirofumi Takeuchi*,Kohei Tahara,Risako Onodera

Gifu Pharmaceutical University,1-25-4 Daigaku-nishi,Gifu 501-1196,Japan

A R T I C L E I N F O

Article history:

Available online 11 November 2015

Drug delivery systems

Liposomes

Administration routes

Absorption

Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design dosage forms to complete effective drug delivery.A variety of investigations have been carried out toward the design of an optimal particulate system in several administration routes for both systemic and topical drug delivery.This presentation demonstrates recent advances in drug delivery using liposomal systems in several administration routes,such as oral,pulmonary,and ocular routes.Use of nano-crystals in delivering drug will be also mentioned.

We succeeded previously in preparing mucoadhesive liposomes by using chitosan as a coating polymer[1].When chitosan-coated liposomes containing a peptide drug such as insulin or calcitonin were orally administered to rats,corresponding pharmacological effects were observed.By decreasing the diameter of liposomes coated with chitosan to submicron size,the pharmacological effects were prolonged extensively.When the intestinal tubes of rats were observed by scanning confocal microscopy after administration of these liposomes,liposome particles were found to have penetrated the enteric mucus layer and then into the mucous layer deeply.

One of recent advances in polymer-coated liposomes for oral administration of peptide drugs is modifcation of coating polymers for increasing the delivery effect.For example,the synergetic effect of carbopol and lectin in the oral administration of calcitonin was confrmed by using carbopol–lectin conjugate for coating the liposomes.Co-formulation of an absorption enhancer,spermine,into the liposomal formulation has also led to improvement in the resultant pharmacological effects of calcitonin formulated to the liposome.It is alsoa recent advance to use the in vivo imaging system(IVIS)for detecting retention of the liposomal system in the intestinal tract non-invasively after oral administration.More recently we have succeeded in detecting the actual absorption of a model material,FITC-dextran,having higher molecular weight up to 10,000 by using the several types of polymer-coated liposomes as carrier.

In characterizing the behavior of polymer-coated liposomes in the lung,the similar effects of polymer-coated liposomes were detected compared with non-coated liposomes[2].We have also confrmed the effectiveness of polymercoated liposomes in the pulmonary administration of liposomal calcitonin.The pharmacological effects after the administration of liposomal calcitonin refected the behavior of the liposomal particles characterized separately.IVIS was successfully used to confrm the good relation between the pharmacological effect and retention of these liposomal particles in the lung as well as in oral administration.

The lack of noninvasive administration method to deliver the drug to posterior segment of eyes is a problem to be solved in treating posterior segment-related diseases such as agerelated macular degeneration(ARMD),diabetic macular edema (DME),etc.,which may cause serious symptoms such as vision impairment and blindness.We have challenged to overcome this issue by using liposomal systems[3].To confrm the usefulness of liposomal systems for delivering drugs to the posterior segments of the eye,we apply liposomal suspension containing a fuorescent marker to the eye in mice.We could detect the stronger fuorescence in the retina when submicronsized liposomes(ssLip)were used as a carrier in the eye drop formulation.This fnding strongly suggested that ssLip can effectively deliver the drug to the posterior part of the eye.Surface modifcation effects have also been confrmed.Very recently, we have demonstrated pharmacological effects of the liposomal eye drops with some APIs and also succeeded in animal scale up to detect the retina delivery with the liposomal systems.

R E F E R E N C E S

[1]Takeuchi H,Yamamoto H,Kawashima Y.Mucoadhesive nanoparticulate systems for peptide drug delivery.Adv Drug Deliver Rev 2001;47:39–54.

[2]Murata T,Nakano K,Tahara K,et al.Pulmonary delivery of elcatonin using surface-modifed liposomes to improve systemic absorption:polyvinyl alcohol with a hydrophobic anchor and chitosan oligosaccharide as effective surface modifers.Eur J Pharm Biopharm 2012;80:340–346.

[3]Hironaka K,Inokuchi Y,Tozuka Y,et al.Design and evaluation of a liposomal delivery system targeting the posterior segment of the eye.J Control Release 2009;136:247–253.

*E-mail address:takeuchi@gifu-pu.ac.jp.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.005

1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).