Basic principles of drug delivery systems – the case of paclitaxel

The fatty acid-based microparticles containing iron oxide nanoparticles and paclitaxel (PAX) are a viable proposition for the treatment of lung cancer. The microparticles inhaled as a dry powder can be guided to selected locations using an external magnetic field, and when accumulated there, the active compound release can be triggered by local hyperthermia. However, this general strategy requires that the active compound is released from microparticles and can reach the targeted cells before microparticles are removed. Isothermal titration calorimetry was used to demonstrate that the components of microparticles were released and transferred to albumins and lipid bilayers. The morphology of the measured particulates was studied with scanning electron microscopy and dynamic light scattering. To determine the cytotoxicity of microparticles, cell culture studies were done. It has been shown that the transfer efficiency depends predominantly on the fatty acid composition of microparticles, which, together with the active ingredient, accumulate predominantly in membrane structures after being released from microparticles and before entering the cytoplasm. The release process is sufficient; hence, paclitaxel-loaded microparticles effectively suppressed the proliferation of A549 human lung epithelial cells of malignant origin (IC 50 values for both lauric acid-based and myristic/palmitic-based microparticles containing paclitaxel were below 0.375 μg/mL), while reference microparticles were noncytotoxic.

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“…The compound with a low log P value can exchange between microparticle and biological structures (membranes or globular proteins). 18 , 26 , 27 …”

Section: Resultsmentioning

confidence: 99%

Evaluation of the In Vitro Stability of Stimuli-Sensitive Fatty Acid-Based Microparticles for the Treatment of Lung Cancer

Dałek

Borowik²,

Reczyńska

et al. 2020

Langmuir

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“…[62][63][64] O comportamento de fase das microemulsões é descrito graficamente por diagramas de fase ternários, elaborado a partir da combinação de três componentes (tensoativo, fase oleosa e fase aquosa) e pseudoternários (os quais apresentam dois tipos de tensoativos, sendo um chamado de cotensoativo, normalmente um álcool de cadeia curta ou média). 53,65 Esses diagramas especificam as fases formadas sob várias condições experimentais determinadas e definem precisamente suas composições. Uma maneira conveniente de representar…”

Section: Microemulsões E Nanoemulsõesunclassified

“…100 A absorção de fármacos no trato gastrointestinal (TGI) ocorre majoritariamente no intestino e há três mecanismos principais pelos quais isso acontece após a molécula atravessar a camada de muco. 65 O primeiro deles é a absorção passiva, em que a molécula atravessa as células da membrana apical para a basolateral e entra na circulação sanguínea; devido à natureza lipídica da membrana plasmática, esse processo permite a penetração de moléculas lipofílicas mas dificulta o transporte de compostos hidrofílicos, além de não ser seletivo. Outro meio passivo utiliza as tight junctions ou junções aderentes, zona em que uma célula se une a outra e permite a passagem de moléculas; esse, por sua vez, tem melhor transporte de moléculas hidrofílicas e também não é seletivo.…”

Section: Nanocarreadores E Peleunclassified

“…O último utiliza transportadores presentes na membrana apical que aceleram o processo de absorção e pode ser tanto passivo, quanto ativo; tem melhor seletividade e é responsável pela maior parte da absorção dos nutrientes. 65 Fármacos muito insolúveis não utilizam nenhum dos transportes citados eficientemente quando administrados na forma livre. Pooja et al 101 explora essa problemática ao incorporar o paclitaxel em um nanocarreador lipídico sólido para administração oral e conjugando em sua superfície lecitina derivada de gérmen de trigo.…”

Section: Nanocarreadores E Peleunclassified

“…Representação microscópica da nanoestruturação de micro e nanoemulsões com destaque para o fato de que as nanoemulsões podem conter gotículas de tamanhos maiores que as microemulsões as possíveis composições de sistemas de microemulsão é construir diagramas de fase como triângulos equiláteros65 (Figura 6).…”

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Abrindo a Caixa De Pandora Dos Nanomedicamentos: Há Realmente Muito Mais ‘Espaço Lá Embaixo

et al. 2020

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Limitations of conventional treatment and dosage forms prompted the investigation of novel approaches that combine efficacy, selectivity and fewer adverse effects. These are the main promises of nanomedicine, generally defined as the application of nanotechnology to the biomedical field. Despite the considerable advances over the years and the large number of publications resulting from the growth of nanomedicine, there are still many hurdles and unknown factors limiting its successful translation from promise to reality. These factors range from the lack of standardization in the terminology and regulations, to the lack of understanding of interactions between nanocarriers and the biological system, and their influence on drug pharmacodynamics. In this manuscript, we aim at presenting and discussing concepts and terminologies used in the nanomedicine field and examining the main types of nanocarriers and their effects to modulate biological barriers and aid drug transport, bioavailability and targeting.

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Evaluation of the efficacy and safety of a new formulation‐lipid emulsion‐based PTX injection: Pharmacokinetics, tissue distributions and anticancer effect on human gastric cancer cells in vitro

Fei

Wang

et al. 2021

Biomedical Chromatography

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Paclitaxel (PTX) is one of the most widely used chemotherapeutic agents. The commercial PTX formulation was based on Cremophor EL and ethanol owing to its poor aqueous solubility. However, Cremophor EL has been shown to cause toxic effects such as life-threatening anaphylaxis. In our study, we diluted PTX in a commercially available 20% (w/v) lipid emulsion (Lip-PTX) in order to avoid Cremophor EL. The purpose of this study was to evaluate the pharmacokinetics and tissue distributions between Lip-PTX and PTX injection. We also investigated the effects of Lip-PTX and PTX injection on human gastric cancer cells HGC-27 by MTT assay. The apoptosis was detected by flow cytometry with Annexin V/propidium iodide (PI) double staining. Furthermore, the safety such as acute toxicity was also assessed. The results showed that PTX in Sprague-Dawley rats administered Lip-PTX exhibited extended half-life, increased clearance (P < 0.05) and smaller area under the concentrationtime curve compared with PTX injection and there was little significant difference in the distribution of PTX in Sprague-Dawley rats or tumor-bearing mice between Lip-PTX and PTX injection. The cells treated with Lip-PTX had a higher percentage of apoptosis and a higher G 2 /M phase ratio, which indicated that the anticancer effect of Lip-PTX was significantly better than that of PTX injection. Moreover, our study highlighted the safety of Lip-PTX. This study demonstrated the feasibility and potential advantages of Lip-PTX for clinical therapy.

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Basic principles of drug delivery systems – the case of paclitaxel

Cited by 84 publications

References 271 publications

Evaluation of the In Vitro Stability of Stimuli-Sensitive Fatty Acid-Based Microparticles for the Treatment of Lung Cancer

Evaluation of the In Vitro Stability of Stimuli-Sensitive Fatty Acid-Based Microparticles for the Treatment of Lung Cancer

Abrindo a Caixa De Pandora Dos Nanomedicamentos: Há Realmente Muito Mais ‘Espaço Lá Embaixo

Evaluation of the efficacy and safety of a new formulation‐lipid emulsion‐based PTX injection: Pharmacokinetics, tissue distributions and anticancer effect on human gastric cancer cells in vitro

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