Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer

Katare, Yogesh K.; Daya, Ritesh P.; Gray, Christal Sookram; Luckham, Roger E.; Bhandari, Jayant; Chauhan, Abhay Singh; Mishra, Ram K.

doi:10.1021/acs.molpharmaceut.5b00402

Cited by 85 publications

(38 citation statements)

References 39 publications

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“…The results of the reduced brain infraction volume were a proof for the activity of siRNA dendrimers as an efficient knock-down of HMGB [212]. In another study, the PAMAM formulation of haloperidol intended for brain targeting showed 100-fold higher solubility with significant brain and plasma concentrations, resulting in a 6.7-fold smaller dose being required to produce a response similar to the intraperitoneal (IP) injection [220]. Additionally, PAMAM showed substantial effects on the nasal absorption of poorly absorbed molecules, namely calcitonin, insulin, and fluorescein isothiocyanate-labelled dextran, as it was pointed out via in vivo studies using a rat model [221].…”

Section: Dendrimersmentioning

confidence: 95%

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

Alshweiat

Ambrus

Csóka

2019

CMC

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There is always a need for alternative and efficient methods of drug delivery. The nasal cavity can be considered as a non-invasive and efficient route of administration. It has been used for local, systemic, brain targeting, and vaccination delivery. Although many intranasal products are currently available on the market, the majority is used for local delivery with fewer products available for the other targets. As nanotechnology utilization in drug delivery has rapidly spread out, the nasal delivery has become attractive as a promising approach. Nanoparticulate systems facilitate drug transportation across the mucosal barrier, protect the drug from nasal enzyme degradation, enhance the delivery of vaccines to the lymphoid tissue of the nasal cavity with an adjuvant activity, and offer a way for peptide delivery into the brain and the systemic circulation, in addition to their potential for brain tumor treatment. This review article aims at discussing the potential benefit of the intranasal nanoparticulate systems, including nanosuspensions, lipid and surfactant, and polymer-based nanoparticles as regards productive intranasal delivery. The aim of this review is to focus on the topicalities of nanotechnology applications for intranasal delivery of local, systemic, brain, and vaccination purposes during the last decade, referring to the factors affecting delivery, regulatory aspects, and patient expectations. This review further identifies the benefits of applying the Quality by Design approaches (QbD) in product development. According to the reported studies on nanotechnology-based intranasal delivery, potential attention has been focused on brain targeting and vaccine delivery with promising outcomes. Despite the significant research effort in this field, nanoparticle-based products for intranasal delivery are not available. Thus, further efforts are required to promote the introduction of intranasal nanoparticulate products that can meet the requirements of regulatory affairs with high patient acceptance.

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Section: Dendrimersmentioning

confidence: 95%

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery

Alshweiat

Ambrus

Csóka

2019

CMC

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“…Furthermore, dendrimers have more efficient paracellular and transcellular transport across the BBB, which makes them ideal carriers for targeting water-insoluble drugs to the brain [122]. Katare et al [123] investigated the efficiency of water-insoluble antipsychotic drug haloperidol via the intranasal route using the PAMAM dendrimer. They demonstrated that the aqueous solubility of haloperidol was increased with the dendrimer-based formulation and showed a significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of the drug.…”

Section: Dendrimers In Central Nervous Systems (Cns) Drug Deliverymentioning

confidence: 99%

Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications

2019

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The European Medicines Agency (EMA) and the Current Good Manufacturing Practices (cGMP) in the United States of America, define excipient as the constituents of the pharmaceutical form other than the active ingredient, i.e., any component that is intended to furnish pharmacological activity. Although dendrimers do not have a pharmacopoeia monograph and, therefore, cannot be recognized as a pharmaceutical excipient, these nanostructures have received enormous attention from researchers. Due to their unique properties, like the nanoscale uniform size, a high degree of branching, polyvalency, aqueous solubility, internal cavities, and biocompatibility, dendrimers are ideal as active excipients, enhancing the solubility of poorly water-soluble drugs. The fact that the dendrimer’s properties are controllable during their synthesis render them promising agents for drug-delivery applications in several pharmaceutical formulations. Additionally, dendrimers can be used for reducing the drug toxicity and for the enhancement of the drug efficacy. This review aims to discuss the properties that turn dendrimers into pharmaceutical excipients and their potential applications in the pharmaceutical and biomedical fields.

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“…Additionally, 6.7 times lower doses of the dendrimer−haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain 39 .…”

Section: Dendrimers In Cns Drug Deliverymentioning

confidence: 65%