Multimodal non-linear optical imaging for the investigation of drug nano-/microcrystal-cell interactions

被引：17

作者：

Darville, Nicolas ^{[1
]}

Saarinen, Jukka ^{[2
]}

Isomaki, Antti ^{[3
]}

Khriachtchev, Leonid ^{[4
]}

Cleeren, Dirk ^{[5
]}

Sterkens, Patrick ^{[6
]}

Van Heerden, Marjolein ^{[6
]}

Annaert, Pieter ^{[1
]}

Peltonen, Leena ^{[2
]}

Santos, Helder A. ^{[2
]}

Strachan, Clare J. ^{[2
]}

Van den Mooter, Guy ^{[1
]}

机构：

[1] Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Drug Delivery & Disposit, Leuven, Belgium

[2] Univ Helsinki, Fac Pharm, Div Pharmaceut Chem & Technol, Helsinki, Finland

[3] Univ Helsinki, Fac Med, Inst Biomed, Anat, Helsinki, Finland

[4] Univ Helsinki, Dept Chem, SF-00100 Helsinki, Finland

[5] Pharmaceut Dev & Mfg Sci, Beerse, Belgium

[6] Janssen Res & Dev, Preclin Dev & Safety, Beerse, Belgium

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2015年 / 96卷

基金：

芬兰科学院; 欧洲研究理事会;

关键词：

Non-linear imaging; CARS microscopy; Paliperidone palmitate; Sustained-release; Drug nano-/microcrystal; RAW; 264.7; macrophages; Long-acting injectable;

D O I：

10.1016/j.ejpb.2015.09.003

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Drug nano-/microcrystals are being used for sustained parenteral drug release, but safety and efficacy concerns persist as the knowledge of the in vivo fate of long-living particulates is limited. There is a need for techniques enabling the visualization of drug nano-/microcrystals in biological matrices. The aim of this work was to explore the potential of coherent anti-Stokes Raman scattering (CARS) microscopy, supported by other non-linear optical methods, as an emerging tool for the investigation of cellular and tissue interactions of unlabeled and non-fluorescent nano-/microcrystals. Raman and CARS spectra of the prodrug paliperidone palmitate (PP), paliperidone (PAL) and several suspension stabilizers were recorded. PP nano-/microcrystals were incubated with RAW 264.7 macrophages in vitro and their cellular disposition was investigated using a fully-integrated multimodal non-linear optical imaging platform. Suitable anti-Stokes shifts (CH stretching) were identified for selective CARS imaging. CARS microscopy was successfully applied for the selective three-dimensional, non-perturbative and real-time imaging of unlabeled PP nano-/microcrystals having dimensions larger than the optical lateral resolution of approximately 400 nm, in relation to the cellular framework in cell cultures and ex vivo in histological sections. In conclusion, CARS microscopy enables the non-invasive and label-free imaging of (sub) micron-sized (pro-)drug crystals in complex biological matrices and could provide vital information on poorly understood nano-/microcrystal-cell interactions in future. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：338 / 348

页数：11

共 57 条

[1]

Zhang L., Gu F.X., Chan J.M., Wang A.Z., Langer R.S., Farokhzad O.C., Nanoparticles in medicine: Therapeutic applications and developments, Clin. Pharmacol. Ther., 83, pp. 761-769, (2007)

[2]

Petros R.A., DeSimone J.M., Strategies in the design of nanoparticles for therapeutic applications, Nat. Rev. Drug Discov., 9, pp. 615-627, (2010)

[3]

Rabinow B.E., Nanosuspensions in drug delivery, Nat. Rev. Drug Discov., 3, pp. 785-796, (2004)

[4]

Junghanns J.-U.A.H., Muller R.H., Nanocrystal technology, drug delivery and clinical applications, Int. J. Nanomed., 3, pp. 295-310, (2008)

[5]

Baert L., Van't Klooster G., Dries W., Francois M., Wouters A., Basstanie E., Iterbeke K., Stappers F., Stevens P., Schueller L., Van Remoortere P., Kraus G., Wigerinck P., Rosier J., Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment, Eur. J. Pharm. Biopharm., 72, pp. 502-508, (2009)

[6]

Van't Klooster G., Hoeben E., Borghys H., Looszova A., Bouche M.-P., Van Velsen F., Baert L., Pharmacokinetics and disposition of rilpivirine (TMC278) nanosuspension as a long-acting injectable antiretroviral formulation, Antimicrob. Agents Chemother., 54, pp. 2042-2050, (2010)

[7]

Samtani M.N., Vermeulen A., Stuyckens K., Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia: A novel once-monthly, long-acting formulation of an atypical antipsychotic, Clin. Pharmacokinet., 48, pp. 585-600, (2009)

[8]

Kramer M., Litman R., Hough D., Lane R., Lim P., Liu Y., Eerdekens M., Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study, Int. J. Neuropsychopharmacol., 13, pp. 635-647, (2010)

[9]

Spreen W.R., Margolis D.A., Pottage J.C., Long-acting injectable antiretrovirals for HIV treatment and prevention, Curr. Opin. HIV AIDS, 8, pp. 565-571, (2013)

[10]

Lindenmayer J., Long-acting injectable antipsychotics: Focus on olanzapine pamoate, Neuropsychiatr. Dis. Treat., 6, pp. 261-267, (2010)

← 1 2 3 4 5 6 →