Curcumin is an antimalarial compound easy to obtain and
inexpensive, having shown little toxicity across a diverse
population. However, the clinical use of this interesting
polyphenol has been ...hampered by its poor oral absorption,
extremely low aqueous solubility and rapid metabolism. In this
study, we have used the anionic copolymer Eudragit(®)
S100 to assemble liposomes incorporating curcumin and containing
either hyaluronan (Eudragit-hyaluronan liposomes) or the
water-soluble dextrin Nutriose(®) FM06
(Eudragit-nutriosomes). Upon oral administration of the
rehydrated freeze-dried nanosystems administered at 25/75 mg
curcumin·kg(−1)·day(−1), only Eudragit-nutriosomes improved the in vivo antimalarial activity of curcumin in a dose-dependent manner, by enhancing the survival of all Plasmodium yoelii-infected mice up to 11/11 days, as compared to 6/7 days upon administration of an equal dose of the free compound. On the other hand, animals treated with curcumin incorporated in Eudragit-hyaluronan liposomes did not live longer than the controls, a result consistent with the lower stability of this formulation after reconstitution. Polymer-lipid nanovesicles hold promise for their development into systems for the oral delivery of curcumin-based antimalarial therapies.
Curcumin is an antimalarial compound easy to obtain and
inexpensive, having shown little toxicity across a diverse
population. However, the clinical use of this interesting
polyphenol has been ...hampered by its poor oral absorption,
extremely low aqueous solubility and rapid metabolism. In this
study, we have used the anionic copolymer Eudragit(®)
S100 to assemble liposomes incorporating curcumin and containing
either hyaluronan (Eudragit-hyaluronan liposomes) or the
water-soluble dextrin Nutriose(®) FM06
(Eudragit-nutriosomes). Upon oral administration of the
rehydrated freeze-dried nanosystems administered at 25/75 mg
curcumin·kg(−1)·day(−1), only Eudragit-nutriosomes improved the in vivo antimalarial activity of curcumin in a dose-dependent manner, by enhancing the survival of all Plasmodium yoelii-infected mice up to 11/11 days, as compared to 6/7 days upon administration of an equal dose of the free compound. On the other hand, animals treated with curcumin incorporated in Eudragit-hyaluronan liposomes did not live longer than the controls, a result consistent with the lower stability of this formulation after reconstitution. Polymer-lipid nanovesicles hold promise for their development into systems for the oral delivery of curcumin-based antimalarial therapies.
The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over their cytotoxic activity would allow ...improving chemotherapy treatments, and light-regulated drugs are well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor of the human dihydrofolate reductase (DHFR), as a photochromic analogue of methotrexate, a widely prescribed chemotherapeutic drug to treat cancer and psoriasis. Quantification of the light-regulated DHFR enzymatic activity, cell proliferation, and in vivo effects in zebrafish show that phototrexate behaves as a potent antifolate in its photoactivated cis configuration and that it is nearly inactive in its dark-relaxed trans form. Thus, phototrexate constitutes a proof-of-concept to design light-regulated cytotoxic small molecules and a step forward to develop targeted anticancer photochemotherapies with localized efficacy and reduced adverse effects.
The adaptation of existing antimalarial nanocarriers to new
Plasmodium stages, drugs, targeting molecules, or encapsulating
structures is a strategy that can provide new
nanotechnology-based, ...cost-efficient therapies against malaria.
We have explored the modification of different liposome
prototypes that had been developed in our group for the targeted
delivery of antimalarial drugs to Plasmodium-infected red blood
cells (pRBCs). These new models include: (i)
immunoliposome-mediated release of new lipid-based
antimalarials; (ii) liposomes targeted to pRBCs with covalently
linked heparin to reduce anticoagulation risks; (iii) adaptation
of heparin to pRBC targeting of chitosan nanoparticles; (iv) use
of heparin for the targeting of Plasmodium stages in the
mosquito vector; and (v) use of the non-anticoagulant
glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate
for pRBC targeting. The results presented indicate that the
tuning of existing nanovessels to new malaria-related targets is
a valid low-cost alternative to the de novo development of
targeted nanosystems.
The adaptation of existing antimalarial nanocarriers to new
Plasmodium stages, drugs, targeting molecules, or encapsulating
structures is a strategy that can provide new
nanotechnology-based, ...cost-efficient therapies against malaria.
We have explored the modification of different liposome
prototypes that had been developed in our group for the targeted
delivery of antimalarial drugs to Plasmodium-infected red blood
cells (pRBCs). These new models include: (i)
immunoliposome-mediated release of new lipid-based
antimalarials; (ii) liposomes targeted to pRBCs with covalently
linked heparin to reduce anticoagulation risks; (iii) adaptation
of heparin to pRBC targeting of chitosan nanoparticles; (iv) use
of heparin for the targeting of Plasmodium stages in the
mosquito vector; and (v) use of the non-anticoagulant
glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate
for pRBC targeting. The results presented indicate that the
tuning of existing nanovessels to new malaria-related targets is
a valid low-cost alternative to the de novo development of
targeted nanosystems.
The adaptation of existing antimalarial nanocarriers to new
Plasmodium stages, drugs, targeting molecules, or encapsulating
structures is a strategy that can provide new
nanotechnology-based, ...cost-efficient therapies against malaria.
We have explored the modification of different liposome
prototypes that had been developed in our group for the targeted
delivery of antimalarial drugs to Plasmodium-infected red blood
cells (pRBCs). These new models include: (i)
immunoliposome-mediated release of new lipid-based
antimalarials; (ii) liposomes targeted to pRBCs with covalently
linked heparin to reduce anticoagulation risks; (iii) adaptation
of heparin to pRBC targeting of chitosan nanoparticles; (iv) use
of heparin for the targeting of Plasmodium stages in the
mosquito vector; and (v) use of the non-anticoagulant
glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate
for pRBC targeting. The results presented indicate that the
tuning of existing nanovessels to new malaria-related targets is
a valid low-cost alternative to the de novo development of
targeted nanosystems.
A nanomedicina envolve a aplicação da melhoria dos diagnósticos médicos e terapia, permitindo o desenvolvimento de fármacos que auxiliem no tratamento de doenças, bem como na aplicação de ...nanopartículas na melhoria da quimioterapia. Por isso, o objetivo deste estudo foi realizar um mapeamento tecnológico sobre as tecnologias utilizadas na aplicação de nanopartículas para melhoria do processo de quimioterapia. A metodologia consiste num estudo exploratório quantitativo, que realizou um levantamento de depósitos de patentes na base de dados European Patent Office (Espacenet). Os resultados mostram que foram poucos depósitos encontrados sobre a aplicação de nanopartículas no processo de quimioterapia, sendo que a China foi o país que mais realizou depósitos, o que mostra que o país vem buscando melhorias nos tratamentos médicos. Ainda, verificou-se que as Universidades foram os maiores depositantes, mostrando que as instituições de ensino estão aprimorando suas pesquisas voltadas a nanotecnologia. Dessa forma, percebe-se que ainda é preciso expandir os estudos voltados a utilização das nanopartículas, visando aprimorar o desenvolvimento de novos produtos, e assim melhorar os processos de diagnóstico e tratamentos médicos.
Combination therapies, where two drugs acting through different mechanisms are administered simultaneously, are one of the most efficient approaches currently used to treat malaria infections. ...However, the different pharmacokinetic profiles often exhibited by the combined drugs tend to decrease treatment efficacy as the compounds are usually eliminated from the circulation at different rates. To circumvent this obstacle, we have engineered an immunoliposomal nanovector encapsulating hydrophilic and lipophilic compounds in its lumen and lipid bilayer, respectively. The antimalarial domiphen bromide has been encapsulated in the liposome membrane with good efficiency, although its high IC50 of ca. 1 µM for living parasites complicates its use as immunoliposomal therapy due to erythrocyte agglutination. The conjugation of antibodies against glycophorin A targeted the nanocarriers to Plasmodium-infected red blood cells and to gametocytes, the sole malaria parasite stage responsible for the transmission from the human to the mosquito vector. The antimalarials pyronaridine and atovaquone, which block the development of gametocytes, have been co-encapsulated in glycophorin A-targeted immunoliposomes. The co-immunoliposomized drugs have activities significantly higher than their free forms when tested in in vitro Plasmodium falciparum cultures: Pyronaridine and atovaquone concentrations that, when encapsulated in immunoliposomes, resulted in a 50% inhibition of parasite growth had no effect on the viability of the pathogen when used as free drugs.
Combination therapies, where two drugs acting through different mechanisms are administered simultaneously, are one of the most efficient approaches currently used to treat malaria infections. ...However, the different pharmacokinetic profiles often exhibited by the combined drugs tend to decrease treatment efficacy as the compounds are usually eliminated from the circulation at different rates. To circumvent this obstacle, we have engineered an immunoliposomal nanovector encapsulating hydrophilic and lipophilic compounds in its lumen and lipid bilayer, respectively. The antimalarial domiphen bromide has been encapsulated in the liposome membrane with good efficiency, although its high IC50 of ca. 1 µM for living parasites complicates its use as immunoliposomal therapy due to erythrocyte agglutination. The conjugation of antibodies against glycophorin A targeted the nanocarriers to Plasmodium-infected red blood cells and to gametocytes, the sole malaria parasite stage responsible for the transmission from the human to the mosquito vector. The antimalarials pyronaridine and atovaquone, which block the development of gametocytes, have been co-encapsulated in glycophorin A-targeted immunoliposomes. The co-immunoliposomized drugs have activities significantly higher than their free forms when tested in in vitro Plasmodium falciparum cultures: Pyronaridine and atovaquone concentrations that, when encapsulated in immunoliposomes, resulted in a 50% inhibition of parasite growth had no effect on the viability of the pathogen when used as free drugs.
Combination therapies, where two drugs acting through different mechanisms are administered simultaneously, are one of the most efficient approaches currently used to treat malaria infections. ...However, the different pharmacokinetic profiles often exhibited by the combined drugs tend to decrease treatment efficacy as the compounds are usually eliminated from the circulation at different rates. To circumvent this obstacle, we have engineered an immunoliposomal nanovector encapsulating hydrophilic and lipophilic compounds in its lumen and lipid bilayer, respectively. The antimalarial domiphen bromide has been encapsulated in the liposome membrane with good efficiency, although its high IC50 of ca. 1 µM for living parasites complicates its use as immunoliposomal therapy due to erythrocyte agglutination. The conjugation of antibodies against glycophorin A targeted the nanocarriers to Plasmodium-infected red blood cells and to gametocytes, the sole malaria parasite stage responsible for the transmission from the human to the mosquito vector. The antimalarials pyronaridine and atovaquone, which block the development of gametocytes, have been co-encapsulated in glycophorin A-targeted immunoliposomes. The co-immunoliposomized drugs have activities significantly higher than their free forms when tested in in vitro Plasmodium falciparum cultures: Pyronaridine and atovaquone concentrations that, when encapsulated in immunoliposomes, resulted in a 50% inhibition of parasite growth had no effect on the viability of the pathogen when used as free drugs.
PDF
