Drug Delivery System (DDS) group

1. What is DDS ?

   Drug delivery system (DDS) is the administration method of pharmaceutics for patients to achieve an attractive therapeutic effect that could not be accomplished by administering the drug only. Goto laboratory has produced a novel drug delivery system by an unique emulsion systems.

2.1. Solid-in-Oil (S/O) nanodispersion

   An emulsion is prepared by mixing two or more immiscible liquids such as water and oil with surfactants. In an emulsion, either of water or oil is dispersed as small particle in the other liquid. Goto laboratory has developed produce a novel drug delivery system by a solid-in-oil nanodispersion, an oil-based nanodispersion of hydrophilic drugs (Fig.1). S/O nanodispersion, in which hydrophilic drugs are coated with hydrophobic surfactant molecules, is prepared by removing the water phase of water-in-oil (W/O) emulsion and has much higher stability and smaller particle size than W/O emulsion. We have ever dispersed various kinds of hydrophilic drugs (such as small molecules, proteins and DNA) in an oil phase as nano-order particles by a S/O nanodispersion technique. Fig.2 represents the physical difference in appearance between native FITC-labeled insulin and its S/O nanodispersion in oil. The FITC-labeled insulin, coating with surfactant in S/O nanodispersion, was highly dispersed in oil as a nano-order dispersion and the transparent solution was obtained (Fig.2(right)). On the other hand, the unmodified FITC-labeled insulin was not dissolved, and precipitated in oil (Fig.2(left)). The mean particle size of the prepared S/O nanodispersion was around 200-300 nm measured by dynamic light scattering. There were no precipitates after storing the S/O nanodispersion at room temperature for 1 month. To prepare S/O nanodispersion, we can use sucrose erucate, which have already been approved as a drug adjuvant.

Fig.1  Schematic illustration of the preparation from a water-in-oil emulsion as a solid particle in a S/O nanodispersion [9]. Fig.2  Comparison of the solubility between native FITC-labeled insulin (left, deposited) and its surfactant complex (right, dispersed) in oil [9].

Fig.3 Fluorescence microscopy
treated with the samples
containing FITC-labeled insulin [9].

2.2. Transcutaneous drug delivery

   A transcutaneous drug delivery, drug delivery through the skin, has many advantages over injection or oral administration because it can avoid first-pass hepatic metabolism and provides the patients with an easier and more convenient route for drug administration. Despite its great potential, the delivery of hydrophilic macromolecules such as peptides and proteins through the skin remains a challenging issue in the development of drug delivery systems. This is mainly due to the intrinsic barrier function of the skin, provided by the highly organized structure of the stratum corneum. Therefore, a number of chemical penetration enhancers have been employed to increase the permeability of the drugs into the skin. However, it has been difficult to achieve therapeutic levels of relatively large drugs (over 500 Da) through intact skin to the systemic circulation by the chemical penetration enhancer alone.

   To overcome these situations, Goto laboratory proposed a novel transcutaneous drug delivery system by a S/O nanodispersion technique. The idea is that the dispersion of the proteins modified with the surfanctant in the oil phase makes the proteins permeable into the skin without any physical enhancers or pre-treatments if a suitable oil with the properties of a chemical penetration enhancer is selected. This concept is novel because to date, almost all studies on transcutaneous delivery of hydrophilic drugs have been based on aqueous vehicles.

   Fig.3 shows fluorescent images of the micropig skin sections treated with the S/O nanodispersion or the control (aqueous solution) containing FITC-labeled insulin. The green fluorescence derived from the FITC-labeled insulin was gradually increased with time when the S/O nanodispersion was applied (Fig.3A-E). By contrast, little fluorescence was observed with the aqueous counterpart (Fig.3F). Further, we demonstrated that proteins up to 40 kDa in molecular weight can be penetrated into the skin by the newly developed S/O nanodispersion technique. Although there still remain the main limitations such as slow permeation through the skin, the S/O nanodispersion technique has a high potential for the creation of a novel transcutaneous protein delivery system.[9]

2.3. Transcutaneous immunization

   Coming soon...

3. Solid-in-Oil-in-Water (S/O/W) emulsion

   We have developed the oral protein delivery by a Solid-in-Oil-in-Water (S/O/W) emulsion. This section is under construction!!

4. Gene delivery

   We have developed the a novel non-viral gene vector by our unique emulsion. This section is under construction!!

5. Collaborative work

   If you are interested in our research, please contact with Prof. Goto or SO pharmaceutical corp..

6. References

  • E. Toorisaka, H. Ono, K. Arimori, N. Kamiya, M. Goto, "Hypoglycemic effect of surfactant-coated insulin solubilized in a novel solid-in-oil-in-water (S/O/W) emulsion" Int. J. Pharm., 252, 271-274 (2003).@

  • ’ʍγ‰hˆκC_ˆκ—DŽqC_’J“T•δCŒγ“‘‰λGAW/O/WŒ^‘½‘ŠƒGƒ}ƒ‹ƒVƒ‡ƒ“’†‚Ι••“ό‚΅‚½RƒKƒ“ά‰–Ž_ƒCƒŠƒmƒeƒJƒ“‚Μ˜R‰k‹@\A‰»ŠwHŠw˜_•ΆWC‘ζ29ŠͺC‘ζ2†Cpp.294-297 (2003)

  • E. Toorisaka, M. Hashida, N. Kamiya, H. Ono, Y. Kokazu, M. Goto, "An enteric-coated dry emulsion formulation for oral insulin delivery" J. Control. Release, 107, 91-96 (2005).

  • H. Piao, N. Kamiya, J. Watanabe, H. Yokoyama, A. Hirata, T. Fujii, I. Shimizu, S. Ito, M. Goto, "Oral delivery of diclofenac sodium using a novel solid-in-oil suspension" Int. J. Pharm., 313, 159-162(2006).

  • H. Piao, N. Kamiya, A. Hirata, H. Yokoyama, T. Fujii, I. Shimizu, S. Ito, M. Goto, "Reduction of gastric ulcerogenicity during multiple administration of diclofenac sodium by a novel solid-in-oil suspension" Pharm. Dev. Technol., 12, 321-325 (2007).

  • H. Yoshiura, M. Hashida, N. Kamiya, M. Goto, "Factors affecting protein release behavior from surfactant.protein complexes under physiological conditions" Int. J. Pharm., 338 174-179 (2007).

  • H. Yoshiura, Y. Tahara, M. Hashida, N. Kamiya, A. Hirata, T. Fujii, M. Goto, "Design and in vivo evaluation of solid-in-oil suspension for oral delivery of human growth hormone" Biochem. Eng. J., 41 106-110 (2008).

  • H. Piao, N. Kamiya, A. Hirata, T. Fujii, I. Shimizu, S. Ito, M. Goto, "A novel solid-in-oil nanosuspension for transdermal delivery of diclofenac sodium" Pharm. Res., 25 896-901 (2008).

  • Y. Tahara, S. Honda, N. Kamiya, H. Piao, A. Hirata, E. Hayakawa, T. Fujii, M. Goto, "A solid-in-oil nanodispersion for transcutaneous protein delivery" J. Control. Release, 131, 14-18 (2008).@[ Fig.1 , Fig.2 , Fig.3 are discribed]

  • “cŒ΄‹`˜NA_’J“T•δAŒγ“‘‰λGAuƒ^ƒ“ƒpƒNŽΏ‚ΜŒo”ηƒfƒŠƒoƒŠ[‚ΜŽΐŒ»vAƒoƒCƒIƒTƒCƒGƒ“ƒX‚ΖƒCƒ“ƒ_ƒXƒgƒŠ[iƒgƒsƒbƒNƒXjA67(2)ŠͺAp.68-70 (2009)

  • Œγ“‘‰λGA‘μ‰hŽ‘A•½“c²•FAŽR‰ΊŒ’A…–μP­A‰ΝŒ΄΄ΝA–φ—TŒ[Au–ς•¨‚ΜƒiƒmƒR[ƒ`ƒ“ƒO(S/O)‹Zp‚π—˜—p‚΅‚½‰»Ο•iASPION CEvA–ŒiMembrane)A34(3)ŠͺAp.159-161@(2009)

  • ‘εŒFˆ€ŽqA–p^‰FA“cŒ΄‹`˜NA_’J“T•δAŒγ“‘‰λGAuSolid-in-Oil‰»‹Zp‚π—˜—p‚΅‚½ƒAƒXƒRƒ‹ƒrƒ“Ž_—U“±‘Μ‚ΜŒo”ηƒfƒŠƒoƒŠ[ƒVƒXƒeƒ€vA–ŒiMembrane)A34(4)ŠͺAp.227-232@(2009)

  • “cŒ΄‹`˜NA_’J“T•δAŒγ“‘‰λGAuS/O‰»‹Zp‚Μ–£—͂ƐV‚΅‚’Œo”η–ς•¨‘—’BƒVƒXƒeƒ€ŽΐŒ»‚Μ‰Β”\«vAPHARM TECH JAPANA25(7)ŠͺAp.1409-1414@(2009)

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