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Author

Koen van der Maaden

Bio: Koen van der Maaden is an academic researcher from Leiden University. The author has contributed to research in topics: Drug delivery & Cationic liposome. The author has an hindex of 16, co-authored 34 publications receiving 1147 citations. Previous affiliations of Koen van der Maaden include Leiden University Medical Center.

Papers
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Journal ArticleDOI
TL;DR: This review describes different production methods for solid and hollow microneedles as well as conditions that influence skin penetration and the view on research and development that is needed to rendermicroneedle-based (trans)dermal drug delivery technologies clinically useful in the near future.

499 citations

Journal ArticleDOI
TL;DR: Cationic liposomes loaded with SLP and poly(I:C) have potential as a powerful therapeutic cancer vaccine formulation and showed an at least 25 fold increase over the T cell frequency induced by the poly( I:C)-adjuvanted soluble SLP.
Abstract: For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated with the TLR3 ligand poly(inosinic-polycytidylic acid) (poly(I:C)) in cationic liposomes consisting of DOTAP and DOPC. The obtained particles were down-sized to about 140 nm (measured by dynamic light scattering) and had a positive zeta-potential of about 26 mV (according to laser Doppler electrophoresis). SLP loading efficiency was about 40% as determined by HPLC. Poly(I:C) loading efficiency was about 50%, as assessed from the fluorescence intensity of fluorescently labelled poly(I:C). Immunogenicity of the liposomal SLP vaccine was evaluated in vitro by its capacity to activate dendritic cells (DCs) and present the processed SLP to SIINFEKL-specific T cells. The effectiveness of the vaccine to activate CD8+ T cells was analysed in vivo after intradermal and subcutaneous immunisation in mice, by measuring antigen-specific T cells in blood and spleens and assessing their functionality by cytokine production and in vivo cytotoxicity. The liposomal formulation efficiently delivered the SLP to DCs in vitro and induced a functional CD8+ T cell immune response in vivo to the CTL epitope present in the SLP. The SLP-specific CD8+ T cell frequency induced by the poly(I:C)-adjuvanted liposomal SLP formulation showed an at least 25 fold increase over the T cell frequency induced by the poly(I:C)-adjuvanted soluble SLP. In conclusion, cationic liposomes loaded with SLP and poly(I:C) have potential as a powerful therapeutic cancer vaccine formulation.

80 citations

Journal ArticleDOI
TL;DR: Preliminary data with commercially available porous microneedles is shown and future directions in this field of research are described, which could be a valuable addition to the othermicroneedle-based drug delivery approaches.
Abstract: In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific and patent literature is reviewed, and we focus on the possibilities and constraints of porous microneedle technologies for dermal drug delivery. Furthermore, we show preliminary data with commercially available porous microneedles and describe future directions in this field of research.

79 citations

Journal ArticleDOI
27 Jul 2015-Langmuir
TL;DR: Topical administration of pH-sensitive microneedles coated with polyelectrolyte multinanolayers of antigens and oppositely charged polymers may be a useful approach for micronedle-based vaccination.
Abstract: The aim of this work was to coat pH-sensitive microneedle arrays with inactivated polio vaccine (IPV) particles and N-trimethyl chitosan chloride (TMC) via electrostatic interactions, and assess the immunogenicity of the vaccine after topical application of the coated microneedles in rats. The surface of 200 μm long microneedles was first chemically modified with pH-sensitive (pyridine) groups and then coated with negatively charged IPV and a positively charged polymer (TMC). To obtain a sufficient high antigen dose, 10 layers of IPV were alternately coated with TMC. The binding of IPV and TMC onto pH-sensitive microneedles was quantified and visualized by using fluorescently labeled TMC and IPV. The release of IPV and TMC from the microneedles was evaluated in ex vivo human skin by fluorescence and the immunogenicity of (unlabeled) IPV was assessed after topical application of the coated microneedles in rats. pH-sensitive microneedles were homogeneously coated with 10 layers of both IPV and TMC, resulting in 45 D antigen units IPV and 700 ng TMC per microneedle array. Fluorescence microscopy imaging revealed that both IPV and TMC were released into ex vivo human skin upon application of the coated microneedles. Finally, in vivo application of IPV-TMC-coated pH-sensitive microneedles in rats led to the induction of IPV specific antibody responses, illustrating that they are practically applicable. Topical administration of pH-sensitive microneedles coated with polyelectrolyte multinanolayers of antigens and oppositely charged polymers may be a useful approach for microneedle-based vaccination.

73 citations

Journal ArticleDOI
TL;DR: A hollow microneedle technology for dermal vaccination that enables fundamental research on factors, such as insertion depth and volume, and insertion angle, on the immune response is successfully developed.
Abstract: Purpose The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination

70 citations


Cited by
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Journal ArticleDOI
TL;DR: Bhushan S. Pattni,† Vladimir V. Chupin,‡ and Vladimir P. Torchilin study the role of phosphorous in the biosynthesis of Membrane Proteins and found that phosphorous binds to polypeptide A in a manner similar to that of polymethine.
Abstract: Bhushan S. Pattni,† Vladimir V. Chupin,‡ and Vladimir P. Torchilin*,†,§,∥ †Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts 02115, United States ‡Laboratory for Advanced Studies of Membrane Proteins, Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

1,124 citations

Journal ArticleDOI
TL;DR: PLA's application as drug-loaded nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities.

637 citations

Journal ArticleDOI
TL;DR: The progress and current status of the transdermal drug delivery field is detailed, numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems are described and particular attention is paid to the emerging field of microneedle technologies.
Abstract: The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.

570 citations

Journal ArticleDOI
TL;DR: A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations.

548 citations

Journal ArticleDOI
TL;DR: This review outlines recent developments in the controlled delivery of insulin, including oral, nasal, pulmonary, transdermal, subcutaneous and closed-loop insulin delivery.
Abstract: Insulin is essential for type 1 and advanced type 2 diabetics to maintain blood glucose levels and prolong lives. The traditional administration requires frequent subcutaneous insulin injections that are associated with poor patient compliance, including pain, local tissue necrosis, infection, and nerve damage. Taking advantage of emerging micro- and nanotechnologies, numerous alternative strategies integrated with chemical approaches for insulin delivery have been investigated. This review outlines recent developments in the controlled delivery of insulin, including oral, nasal, pulmonary, transdermal, subcutaneous and closed-loop insulin delivery. Perspectives from new materials, formulations and devices at the micro- or nano-scales are specifically surveyed. Advantages and limitations of current delivery methods, as well as future opportunities and challenges are also discussed.

347 citations