Controlling drug release by introducing lipase inhibitor within a lipid formulation

Murshed, Mubtasim; Pham, Anna C.; Vithani, Kapilkumar; Salim, Malinda; Boyd, Ben J.

doi:10.1016/j.ijpharm.2022.121958

Cited by 9 publications

(6 citation statements)

References 38 publications

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“…As PBA at the concentration of >100 μM has been shown to inhibit more than 60% of lipase activity, 41 the result strongly suggests the role of lipase in macrophagemediated PTMC erosion. In addition, orlistat (also known as tetrahydrolipstatin), a potent drug that inhibits the catalytic activity of lipase in monocyte cell-derived macrophages, 42,43 also demonstrated a similar dose-related suppression on PTMC erosion in the macrophages' incubation (Figure 8C,F). Therefore, several potential factors to the biodegradation of PTMC raised to date were detected at the cellular level.…”

Section: Factors Secreted By Macrophages In Eroding Ptmcmentioning

confidence: 80%

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

Wang

Zhao

et al. 2023

Biomacromolecules

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Poly(trimethylene carbonate) (PTMC), as one of the representatives of biodegradable aliphatic polycarbonates, has been found to degrade in vivo via surface erosion. This unique degradation behavior and the resulting nonacidic products make it more competitive with aliphatic polyesters (e.g., polylactide) in clinical practice. However, this surface degradation mechanism is complicated and not fully understood to date despite the findings that several reactive oxygen species and enzymes can specifically degrade PTMC in vitro. Herein, the biodegradation mechanism of PTMC was investigated by using possible degradation factors, distinct cell lines, and the inhibitors of these factors. The results demonstrate that PTMC undergoes a specific macrophage-mediated erosion. Macrophages tend to fuse into giant cells and elicit a typical inflammatory response by releasing proinflammatory cytokines. In addition, macrophages are suggested to primarily secrete enzymes (lipase specifically) to erode the PTMC bulk extracellularly as inhibiting their activity effectively prevented this eroding process. The clarification of the biodegradation mechanism in this work suggests that the degradation of PTMC highly depends on the foreign body response. Thus, it reminds the researchers to consider the effect of the microenvironment on the degradation and drug release of PTMC-based implantation devices and localized drug delivery systems.

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Section: Factors Secreted By Macrophages In Eroding Ptmcmentioning

confidence: 80%

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

Wang

Zhao

et al. 2023

Biomacromolecules

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“…It is logical to assume that such formulations, delivering the drug in its lipid-based carrier, are preferred to increase bioavailability. However, when the lipid formulation undergoes enzymatic degradation, drug precipitation may occur, resulting in a negligible effect on drug absorption [22,23]. Enzymatic degradation might be due to colonic fermentation as well.…”

Section: Oral Route 21 In Vitro Methodsmentioning

confidence: 99%

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

et al. 2023

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Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers.

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“…As lipases são essenciais para a digestão de gorduras e a inibição dessas enzimas pelo Orlistate pode levar a alterações gastrointestinais. Este mecanismo mostra que a supressão da atividade lipásica pode causar desequilíbrios na digestão de gorduras, potencialmente contribuindo para a inflamação (Murshed et al, 2022).…”

Section: Mediadores Envolvidosunclassified

“…Esta dose é geralmente considerada um equilíbrio ideal entre eficácia e tolerabilidade. Entretanto, há uma variação significativa na resposta individual, o que pode afetar a incidência de inflamação gastrointestinal (Candela et al 2021) (Murshed et al, 2022).…”

Section: Efeitos Em Diferentes Dosesunclassified

Panorama das publicações científicas (2019-2023) sobre Inflamação Gastrointestinal associada à Orlistate: Uma revisão integrativa da literatura

Silva,

Redig,

Furtado

et al. 2024

RSD

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Objetivo: Realizar uma revisão integrativa da literatura para avaliar o papel do Orlistate na indução de inflamação gastrointestinal, identificar os mecanismos subjacentes e fornecer uma visão abrangente dos estudos existentes sobre o assunto no período de 2019 a 2023. Metodologia: Segue uma abordagem de revisão integrativa, com o propósito de agregar os resultados de pesquisas publicadas e apresentá-los a partir de uma questão de pesquisa. Foram realizadas buscas em diversas bases de dados, incluindo o MEDLINE (via portal PubMed da National Library of Medicine), LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), EMBASE, SCOPUS e Web of Science. Resultados: 11 publicações foram selecionadas para inclusão no estudo. Este número relativamente pequeno de estudos incluídos, em comparação ao número inicial (195) de publicações identificadas, reflete a rigidez dos critérios de seleção e a ênfase na qualidade e pertinência dos dados. Quanto as categorias, identificou-se Biomarcadores de Inflamação, Mediadores Envolvidos, Efeitos em Diferentes Doses e Impacto da Duração do Tratamento. Conclusão: Conclui-se que a personalização do tratamento, considerando as características individuais e a resposta do paciente, é fundamental para maximizar os benefícios e minimizar os efeitos adversos.

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Controlling drug release by introducing lipase inhibitor within a lipid formulation

Cited by 9 publications

References 38 publications

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

Panorama das publicações científicas (2019-2023) sobre Inflamação Gastrointestinal associada à Orlistate: Uma revisão integrativa da literatura

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