Electrospun core/shell nanofibers as designed devices for efficient Artemisinin delivery

Herein, engineered electrospun core/shell nanofibers containing different percents of Artemisinin (ART) were developed as new systems for drug administration in malaria and prostate cancer fields. In order to preserve drug bioavailability, a hyperbranched poly(butylene adipate) (HB), acting as crystal suppressant of ART, was employed as core material. Poly(vinylpirrolidone) (PVP) was selected as shell material being easy processable, self-standing and effective in facilitating ART release in aqueous medium. The investigation was carried out considering both the technological and biological aspects, by first assessing the release capability of nanofibers, and successively by evaluating the pharmacological activity of encapsulated ART against cancer cell proliferation and malarial parasites (P. falciparum) growth through in vitro tests. Inferred results confirmed the formation of nanofibers with an effective drug-loaded capability. Moreover, the different hydrophobic character of the HB and PVP enabled the triggering of the drug release and the control on its solubility in the aqueous medium

In vitro and in vivo anti‑malarial activity of plants from the Brazilian Amazon

Submitted by Nuzia Santos ([email protected]) on 2016-07-08T18:45:22Z No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2016-07-08T19:00:53Z (GMT) No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5)Made available in DSpace on 2016-07-08T19:00:53Z (GMT). No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5) Previous issue date: 2015Made available in DSpace on 2016-07-22T13:23:06Z (GMT). No. of bitstreams: 3 ve_Lima_Renata_INVitro_CPqRR_2015.pdf.txt: 78136 bytes, checksum: 163d252edb75adfcdde79e41ea296080 (MD5) ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2015Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil / Centro Universitário Lima do Norte. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil / Centro Universitário Lima do Norte. Manaus, AM, Brasil.Universidade Estadual do Amazonas. Escola Superior de Ciências da Saúde. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.Embrapa Amazônia Ocidental. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Instituto Nacional de Pesquisas da Amazônia Laboratório de Malária e Dengue, Coordenação de Sociedade, Ambiente. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.BACKGROUND: The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. METHODS: Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice. RESULTS: High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71% suppression of P. berghei parasitaemia versus untreated controls). CONCLUSIONS: Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present