A surface modification of clozapine-loaded nanocapsules improves their efficacy: A study of formulation development and biological assessment

Vieira, Simone Machado; Michels, Luana Roberta; Roversi, Katiane; Metz, Vinícia Garzella; Moraes, Barbra Katyuschya Sanches; Piegas, Eduarda Martini; Freddo, Rodrigo José; Gündel, André; Costa, Teresa Dalla; Bürger, Marilise Escobar; Colomé, Letícia Marques; Haas, Sandra Elisa

doi:10.1016/j.colsurfb.2016.05.065

Cited by 32 publications

(13 citation statements)

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“…16,48,49 The cationic zeta potential has an important role in the electrostatic interaction with the cell membrane, allowing a greater affinity between particle-membrane and, consequently, improved biological performance. 22,50 Drug loading was almost 100% for all NCs (100.1-104.1%). This was not observed for NS, which had a recovery of around 80% (81.5 ± 4.9% for NSP80 and 89.6 ± 4% for NCEUD).…”

Section: Technological Evaluation Of Quinine-loaded Nanocapsulesmentioning

confidence: 99%

“…The pH values were determined using a potentiometer (HANNA ® ). 22 The concentration of QN nanoparticles was assayed by HPLC using a previously validated method. 26 The analysis was performed on a Shimadzu LC system (Kyoto, Japan), which consisted of a LC-20AT pump, an SPD-M20A photodiode array (PDA) detector, a CBM-20A system controller, a DGU-20A3 degasser, and a SIL-20A autosampler.…”

Section: Preparation and Characterization Of Quinine-loaded Nanopartimentioning

confidence: 99%

“…Surface modifications of nanoparticles using various agents can help to improve properties for different applications in the field of nanotechnology. [18][19][20] This has been widely explored, and shown to modify the in vitro and in vivo performance of drugs, 21,22 including the efficiency of intravenously administered QN. Thus, it may be possible to generate changes in hydrophilicity/hydrophobicity and the surface charge of systems, inducing different interactions with the living system and consequently a biological response associated with drugs.…”

Section: Introductionmentioning

confidence: 99%

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<p>Effects of Surface Characteristics of Polymeric Nanocapsules on the Pharmacokinetics and Efficacy of Antimalarial Quinine</p>

Michels¹,

Maciel²,

Nakama³

et al. 2019

IJN

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Introduction: The surface charge of nanoparticles, such as nanospheres (NS) and nanocapsules (NC), has been studied with the purpose of improving the in vivo performance of drugs. The aim of this study was to develop, characterize, and evaluate the in vitro antimalarial efficacy of NCP80 and NSP80 (polysorbate coated) or NCEUD and NSEUD (prepared with Eudragit RS 100) loading quinine (QN). Methods: Formulations were prepared by the nanoprecipitation method, followed by wide physicochemical characterization. Antimalarial activity in Plasmodium berghei-infected mice and populational pharmacokinetics (PopPK) in rats were evaluated. Results: The formulations showed a nanometric range (between 138 ± 3.8 to 201 ± 23.0 nm), zeta potential (mV) of −33.1 ± 0.7 (NCP80), −30.5 ± 1 (UNCP80), −25.5 ± 1 (NSP80), −20 ± 0.3 (UNSP80), 4.61 ± 1 (NCEUD), 14.1 ± 0.9 (UNCEUD), 2.86 ± 0.3 (NSEUD) and 2.84 ± 0.6 (UNSEUD), content close to 100%, and good QN protection against UVA light. There was a twofold increase in the penetration of QN into infected erythrocytes with NC compared to that with NS. There was a significant increase in t 1/2 for all NC evaluated compared to that of Free-QN, due to changes in Vdss. PopPK analysis showed that NCP80 acted as a covariate to Q (intercompartmental clearance) and V2 (volume of distribution in the peripheral compartment). For NCEUD, V1 and Q were modified after QN nanoencapsulation. Regarding in vivo efficacy, NCEUD increased the survival of mice unlike Free-QN. Conclusion: Cationic nanocapsules modified the pharmacology of QN, presenting a potential alternative for malaria treatment.

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Section: Technological Evaluation Of Quinine-loaded Nanocapsulesmentioning

confidence: 99%

Section: Preparation and Characterization Of Quinine-loaded Nanopartimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Effects of Surface Characteristics of Polymeric Nanocapsules on the Pharmacokinetics and Efficacy of Antimalarial Quinine</p>

Michels¹,

Maciel²,

Nakama³

et al. 2019

IJN

Self Cite

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“…Vieira et al modified poly‐(ε‐caprolactone) based nanoparticles with polysorbate 80 (P80), polyethylene glycol (PEG), or Chitosan (CS). All three formulations gave nanoparticles that had diameters between 100 and 500 nm [Vieira et al, ]. Nanoparticles coated with P80, PEG, or CS were found to mitigate CZP‐associated side effects in mice.…”

Section: Atypical Antipsychotic Deliverymentioning

confidence: 99%

Delivery of Antipsychotics with Nanoparticles

Sun

Chen

Liu

et al. 2016

Drug Development Research

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Preclinical Research Psychosis remains one of the most challenging health problems for society, affecting hundreds of millions of people worldwide. Although current antipsychotics can alleviate the symptoms of psychosis, they are still far away from being perfect, often causing significant and even fatal side effects such as involuntary movement disorders and metabolic syndrome. With the lack of precise knowledge of the underlying mechanisms of psychosis, a rational approach to improve the efficiency of current antipsychotics is by nanoparticle-based administration. Nanoparticles with the size of 1-500 nm can be used in drug formulations to pass through many biological barriers including the blood-brain barrier, which makes them excellent candidates for the delivery of antipsychotics. Besides that, nanoparticles loaded with antipsychotics can solve the common aqueous solubility issues for most brain targeting drugs, and enable a slow-release profile for the encapsulated drugs. This research overview provides a brief summary and discussion of the progress and development in the delivery of antipsychotics with nanoparticle formulations over the past five years (2011-2016). Drug Dev Res 77 : 393-399, 2016. © 2016 Wiley Periodicals, Inc.

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“…Considering the above features of CLO, it is not surprising that there is a need to find a more efficient and safer route of administration of this drug Therefore, the development of new form of CLO, allowing its controlled release, which may improve its therapeutic potential, is one of the most significant topics for modern neuroscience. Recently, several different nanoformulations of CLO have been presented (Moraes et al 2016;Kirbay et al 2017;Vieira et al 2016;Panda et al 2016;da Costa Güllich et al 2015). The findings show that various CLO nanoformulations may lead to decrease of side effects suggesting that the drug, when loaded to different nanocapsules, is able to mitigate the harmful effects (da Costa Güllich et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Encapsulation of clozapine into polycaprolactone nanoparticles as a promising strategy of the novel nanoformulation of the active compound

et al. 2019

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Clozapine (CLO), an atypical antipsychotic used in the clinic for treatment of schizophrenia, has a well-known efficacy, but its general use in clinical practice is limited because of the risk of serious side effects. Therefore, in the present work, we focused on the encapsulation of CLO into polymeric polycaprolactone nanoparticles (PCL NPs) and studies of interactions of this nanoformulation with model cells. Two types of clozapine PCL NPs (CLO-PCL NPs), pegylated and non-pegylated, were obtained by nanoemulsion templating method. The complex interactions of these NPs with three model cell lines (HEK 293, human embryonic kidney cell line; RAW 264.7, murine macrophage cell line; hCMEC/D3, model of blood-brain barrier, BBB) were studied. Cell viability, cellular uptake of NPs, NO release, expression of proinflammatory agents and transcytosis experiments were performed. Pegylated CLO-PCL NPs showed better results in the tests performed in the present study, in comparison to non-pegylated ones: they are not toxic to model cells; pegylated outer surface protected from their fast uptake by macrophages; they were not immunogenic; transcytosis experiments pointed to their ability to cross a model BBB. The results obtained in the present study indicate that pegylated CLO-PCL NPs are promising carrier for antipsychotic drugs directed to cross BBB. The experiments were conducted using only in vitro models but they provide valuable data in the field of nanotechnology which can be used in novel molecular pharmacology.

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A surface modification of clozapine-loaded nanocapsules improves their efficacy: A study of formulation development and biological assessment

Cited by 32 publications

References 50 publications

<p>Effects of Surface Characteristics of Polymeric Nanocapsules on the Pharmacokinetics and Efficacy of Antimalarial Quinine</p>

<p>Effects of Surface Characteristics of Polymeric Nanocapsules on the Pharmacokinetics and Efficacy of Antimalarial Quinine</p>

Delivery of Antipsychotics with Nanoparticles

Encapsulation of clozapine into polycaprolactone nanoparticles as a promising strategy of the novel nanoformulation of the active compound

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