Nanomedicines and nanocarriers in clinical trials: surfing through regulatory requirements and physico-chemical critical quality attributes

Dri, Diego Alejandro; Rinaldi, Federica; Carafa, Maria; Marianecci, Carlotta

doi:10.1007/s13346-022-01262-y

Cited by 12 publications

(14 citation statements)

References 25 publications

(20 reference statements)

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“…However, some distinctive morphological characteristics of the internal morphology should also be taken into account as additional proposed parameters to be considered for the characterization of nanomedicines. For example, the bilayer characteristics, if a bilayer is present, could be one of them [ 46 ]. For example, in cases of lipidic nanoparticles carrying nucleic acids, a highly organized internal morphology with cavities is usually observed.…”

Section: Discussionmentioning

confidence: 99%

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

Chountoulesi,

Pippa,

Forys

et al. 2024

Polymers

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The combination of phospholipids and block-copolymers yields advanced hybrid nanoparticles through the self-assembly process in an aqueous environment. The physicochemical features of the lipid/polymer components, like the lipid–polymer molar ratio, the macromolecular architecture of the block copolymer, the main transition temperature of the phospholipid, as well as the formulation and preparation protocol parameters, are some of the most crucial parameters for the formation of hybrid lipid/polymer vesicles and for the differentiation of their morphology. The morphology, along with other physicochemical nanoparticle characteristics are strictly correlated with the nanoparticle’s later biological behavior after being administered, affecting interactions with cells, biodistribution, uptake, toxicity, drug release, etc. In the present study, a structural evaluation of hybrid lipid–polymer nanoparticles based on cryo-TEM studies was undertaken. Different kinds of hybrid lipid–polymer nanoparticles were designed and developed using phospholipids and block copolymers with different preparation protocols. The structures obtained ranged from spherical vesicles to rod-shaped structures, worm-like micelles, and irregular morphologies. The obtained morphologies were correlated with the formulation and preparation parameters and especially the type of lipid, the polymeric guest, and their ratio.

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Section: Discussionmentioning

confidence: 99%

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

Chountoulesi,

Pippa,

Forys

et al. 2024

Polymers

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“…To our knowledge, there are no specific regulatory guidelines for radiation nanomedicines. However, guidelines for nanomedicines have been published by the U.S. FDA (Paradise 2019 ; Thapa and Kim 2023 ) and the European Medicines Agency (EMA) and Health Canada (Dri et al 2023 ). The quality requirements for nanomedicines vary between regulatory agencies, but generally include evaluation of the physico-chemical properties of the NPs such as particle size and morphology, stability, surface charge, drug loading and release, sterility and endotoxins testing and toxicity assessment (Anonymous 2022 ; Dri et al 2023 ).…”

Section: Main Textmentioning

confidence: 99%

“…However, guidelines for nanomedicines have been published by the U.S. FDA (Paradise 2019 ; Thapa and Kim 2023 ) and the European Medicines Agency (EMA) and Health Canada (Dri et al 2023 ). The quality requirements for nanomedicines vary between regulatory agencies, but generally include evaluation of the physico-chemical properties of the NPs such as particle size and morphology, stability, surface charge, drug loading and release, sterility and endotoxins testing and toxicity assessment (Anonymous 2022 ; Dri et al 2023 ). Radiation nanomedicines would require additional tests for measurement of radiochemical purity (RCP) and radionuclide purity (RNP), stability against loss of radiometal in serum, organ dosimetry and radiation toxicity.…”

Section: Main Textmentioning

confidence: 99%

Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape

Reilly,

Georgiou,

Brown

et al. 2024

EJNMMI radiopharm. chem.

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Background Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups. Main body Gold nanoparticles were studied initially for radiosensitization of breast cancer to X-radiation therapy. These nanoparticles were labeled with 111In to assess their biodistribution after intratumoural vs. intravenous injection. Intravenous injection was limited by high liver and spleen uptake and low tumour uptake, while intratumoural injection provided high tumour uptake but low normal tissue uptake. Further, [111In]In-labeled gold nanoparticles modified with trastuzumab and injected iintratumourally exhibited strong tumour growth inhibition in mice with subcutaneous HER2-positive human breast cancer xenografts. In subsequent studies, strong tumour growth inhibition in mice was achieved without normal tissue toxicity in mice with human breast cancer xenografts injected intratumourally with gold nanoparticles labeled with β-particle emitting 177Lu and modified with panitumumab or trastuzumab to specifically bind EGFR or HER2, respectively. A nanoparticle depot (nanodepot) was designed to incorporate and deliver radiolabeled gold nanoparticles to tumours using brachytherapy needle insertion techniques. Treatment of mice with s.c. 4T1 murine mammary carcinoma tumours with a nanodepot incorporating [90Y]Y-labeled gold nanoparticles inserted into one tumour arrested tumour growth and caused an abscopal growth-inhibitory effect on a distant second tumour. Convection-enhanced delivery of [177Lu]Lu-AuNPs to orthotopic human glioblastoma multiforme (GBM) tumours in mice arrested tumour growth without normal tissue toxicity. Other groups have explored radiation nanomedicines for cancer treatment in preclinical animal tumour xenograft models using gold nanoparticles, liposomes, block copolymer micelles, dendrimers, carbon nanotubes, cellulose nanocrystals or iron oxide nanoparticles. These nanoparticles were labeled with radionuclides emitting Auger electrons (111In, 99mTc, 125I, 103Pd, 193mPt, 195mPt), β-particles (177Lu, 186Re, 188Re, 90Y, 198Au, 131I) or α-particles (225Ac, 213Bi, 212Pb, 211At, 223Ra). These studies employed intravenous or intratumoural injection or convection enhanced delivery. Local administration of these radiation nanomedicines was most effective and minimized normal tissue toxicity. Conclusions Radiation nanomedicines have shown great promise for treating cancer in preclinical studies. Local intratumoural administration avoids sequestration by the liver and spleen and is most effective for treating tumours, while minimizing normal tissue toxicity.

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“…Notwithstanding, regulatory science 3 faces important challenges to develop standards and guidelines applicable to nanotechnological breakthroughs to facilitate their translation into society ( 8 , 9 ). Proof of this is the absence of harmonized regulatory definitions of key terms such as nanomaterials, nanotechnology, nanopharmaceutical, or nanomedicine and classification systems for NHPs, which is a relevant limitation for the interoperability of the different stakeholders (regulators, academic researchers, physicians, and the industry) ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Classification system for nanotechnology-enabled health products with both scientific and regulatory application

Rodríguez-Gómez,

Penon,

Monferrer

et al. 2023

Front. Med.

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The lack of specific regulatory guidelines for nanotechnology-enabled health products (NHPs) is hampering development and patient access to these innovative technologies. Namely, there is an urgent need for harmonized regulatory definitions and classification systems that allow establishing a standardized framework for NHPs regulatory assessment. In this work, a novel classification system for NHPs is proposed. This classification can be applied for sorting nano-based innovations and regulatory guidelines according to the type of NHPs they address. Said methodology combines scientific and regulatory principles and it is based on the following criteria: principal mode of action, chemical composition, medical purpose and nanomanufacturing approach. This classification system could serve as a useful tool to sensor the state of the art of NHPs which is particularly useful for regulators to support strategy development of regulatory guidelines. Additionally, this tool would also allow manufacturers of NHPs to align their development plans with their applicable guidelines and standards and thus fulfill regulators expectations.

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Nanomedicines and nanocarriers in clinical trials: surfing through regulatory requirements and physico-chemical critical quality attributes

Cited by 12 publications

References 25 publications

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

Structure-Based Evaluation of Hybrid Lipid–Polymer Nanoparticles: The Role of the Polymeric Guest

Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape

Classification system for nanotechnology-enabled health products with both scientific and regulatory application

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