Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders

del Moral, Maria; Loeck, Maximilian; Muntimadugu, Eameema; Vives, Guillem; Pham, Vy; Pfeifer, Peter; Battaglia, Giuseppe; Muro, Silvia

doi:10.3390/jfb14090440

Cited by 3 publications

(2 citation statements)

References 72 publications

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“…Del Moral et al . examined the PLGA NP technique, evaluating the efficacy of NPs based on their lactide and glycolide composition 110 . Their findings indicate a preference for the 60:40 NP formulation due to its superior encapsulation efficiency.…”

Section: Treatmentmentioning

confidence: 99%

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From pathological mechanisms in Krabbe disease to cutting‐edge therapy: A comprehensive review

Ketata,

Ellouz

2024

Neuropathology

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Since its initial documentation by Knud Krabbe in 1916, numerous studies have scrutinized the characteristics of Krabbe disease (KD) until the identification of the mutation in the GALC gene. In alignment with that, we investigated the natural history of KD spanning eight decades to gain a deeper understanding of the evolutionary trajectory of its mechanisms. Through our comprehensive analysis, we unearthed additional novel elements in molecular biology involving the micropathological mechanism of the disease. This review offers an updated perspective on the metabolic disorder that defines KD. Recently, extracellular vesicles (EVs), autophagy impairment, and α‐synuclein have emerged as pivotal players in the neuropathological processes. EVs might serve as a cellular mechanism to avoid or alleviate the detrimental impacts of excessive toxic psychosine levels, and extracting EVs could contribute to synapse dysfunction. Autophagy impairment was found to be independent of psychosine and reliant on AKT and B‐cell lymphoma 2. Additionally, α‐synuclein has been recognized for inducing cellular death and dysfunction in common biological pathways. Our objective is to assess the effectiveness of advanced therapies in addressing this particular condition. While hematopoietic stem cells have been a primary treatment, its administration proves challenging, particularly in the presymptomatic phase. In this review, we have compiled information from over 10 therapy trials, comparing them based on their benefits and disadvantage.

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Section: Treatmentmentioning

confidence: 99%

“…Their findings indicate a preference for the 60:40 NP formulation due to its superior encapsulation efficiency. Additionally, 50:50 NPs present a feasible alternative, while the increased stability of 75:25 NPs may pose a challenge to lysosomal function 110 . Herzeg et al .…”

Section: Treatmentmentioning

confidence: 99%

From pathological mechanisms in Krabbe disease to cutting‐edge therapy: A comprehensive review

Ketata,

Ellouz

2024

Neuropathology

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Preclinical evaluation of polymer encapsulated carbon-based nano and microparticles for sentinel lymph node tattooing

Baselga,

Güemes,

Arruebo

et al. 2024

Sci Rep

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Selective sentinel lymph node biopsy (SNLB) is the standard method for detecting regional metastases in breast cancer patients. Identifying affected axillary lymph nodes before neoadjuvant treatment is crucial, as such treatment may alter drainage pathways and lymph node morphology, hindering the identification of sentinel lymph nodes. The use of carbon-based tattooing on sentinel lymph nodes (SLN) has been employed as a permanent tattooing method in clinical studies of Targeted Axillary Dissection (TAD), aiding in the SLN identification during surgery. Our study introduces a new method of lymph node tattooing based on poly lactic-co-glycolic (PLGA) particles with encapsulated carbon. This strategy substantially improves tattooing efficiency over single carbon suspensions currently used in clinical studies. We synthesized and characterized carbon-loaded PLGA micro- and nanoparticles, experimentally assessing their biological impact on porcine lymph nodes. The effect of particles’ size and concentration was evaluated over time (from 1 to 16 weeks). Light and electron microscopy studies were conducted to characterize the cellular effects induced by the presence of these particles. Our findings reveal that the diverse physicochemical parameters of the particles interact differently with the lymphatic tissue, influencing their biodistribution within the lymph nodes and the intensity of the inflammatory response. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-80931-z.

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Melanin-Based Nanoparticles for Lymph Node Tattooing: Experimental, Histopathological and Ultrastructural Study

Baselga,

Güemes,

Yus

et al. 2024

Nanomaterials

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In breast cancer, Targeted Axillary Dissection (TAD) allows for the selective excision of the sentinel lymph node (SLN) during primary tumor surgery. TAD consists of the resection of labelled SLNs prior to neoadjuvant chemotherapy (NACT). Numerous clinical and preclinical studies have explored the use of carbon-based colloids for SLN tattooing prior to NACT. However, carbon vectors show varying degrees of inflammatory reactions and, in about one fifth of cases, carbon particles migrate via the lymphatic pathway to other nodes, causing the SLN to mismatch the tattooed node. To overcome these limitations, in this study, we explored the use of melanin as a staining endogenous pigment. We synthesized and characterized melanin-loaded polymeric nanoparticles (Mel-NPs) and used them to tattoo lymph nodes in pig animal models given the similarity in the size of the human and pig nodes. Mel-NPs tattooed lymph nodes showed high identification rates, reaching 83.3% positive identification 16 weeks after tattooing. We did not observe any reduction in the identification as time increased, implying that the colloid is stable in the lymph node tissue. In addition, we performed histological and ultrastructural studies to characterize the biological behavior of the tag. We observed foreign-body-like granulomatous inflammatory responses associated with Mel-NPs, characterized by the formation of multinucleated giant cells. In addition, electron microscopy studies showed that uptake is mainly performed by macrophages, and that macrophages undergo cellular damage associated with particle uptake.

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Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders

Cited by 3 publications

References 72 publications

From pathological mechanisms in Krabbe disease to cutting‐edge therapy: A comprehensive review

From pathological mechanisms in Krabbe disease to cutting‐edge therapy: A comprehensive review

Preclinical evaluation of polymer encapsulated carbon-based nano and microparticles for sentinel lymph node tattooing

Melanin-Based Nanoparticles for Lymph Node Tattooing: Experimental, Histopathological and Ultrastructural Study

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