Optimizing biodegradable nanoparticle size for tissue-specific delivery

Mandl, Hanna K.; Quijano, Elias; Suh, Hee-Won; Sparago, Emily; Oeck, Sebastian; Grun, Molly K; Glazer, Peter M.; Saltzman, W. Mark

doi:10.1016/j.jconrel.2019.09.020

Cited by 48 publications

(32 citation statements)

References 56 publications

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“… 12 Designing particles to improve localization in a particular tissue can be achieved through careful consideration of parameters such as size, shape, surface chemistry, and mechanical stiffness. 11 , 12 , 47 − 49 …”

Section: Spatial Control Of Theranostic Systemsmentioning

confidence: 99%

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

2021

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Materials that respond to endogenous stimuli are being leveraged to enhance spatiotemporal control in a range of biomedical applications from drug delivery to diagnostic tools. The design of materials that undergo morphological or chemical changes in response to specific biological cues or pathologies will be an important area of research for improving efficacies of existing therapies and imaging agents, while also being promising for developing personalized theranostic systems. Internal stimuli-responsive systems can be engineered across length scales from nanometers to macroscopic and can respond to endogenous signals such as enzymes, pH, glucose, ATP, hypoxia, redox signals, and nucleic acids by incorporating synthetic bio-inspired moieties or natural building blocks. This Review will summarize response mechanisms and fabrication strategies used in internal stimuli-responsive materials with a focus on drug delivery and imaging for a broad range of pathologies, including cancer, diabetes, vascular disorders, inflammation, and microbial infections. We will also discuss observed challenges, future research directions, and clinical translation aspects of these responsive materials.

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Section: Spatial Control Of Theranostic Systemsmentioning

confidence: 99%

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

2021

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“…Compared with traditional drug delivery systems, the use of nanocarriers displays many advantages, e.g., a prolonged drug half-life, controlled release and enhanced drug absorption, improved drug stability, limited drug side effects, and targeted delivery [ 68 ]. For this reason, nanocarrier-based drug delivery systems may represent a novel strategy for the treatment of several human diseases, including tumors, diabetes, and others [ 69 ]. Not all types of nanocarriers are reliable as drugs carriers; indeed, an ideal nanocarrier as a drug delivery system needs to be modified or functionalized and should fulfill specific criteria.…”

Section: Nanotechnologies and Vitb12mentioning

confidence: 99%

Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients’ Lives, and Reduce Costs

et al. 2021

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Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients’ lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Furthermore, the high-dose injection of VitB12 does not ensure a constant dosage, while the oral route allows only 1.2% of the vitamin to be absorbed in human beings. Nanocarriers are promising nanotechnology that can enable therapies to be improved, reducing side effects. Today, nanocarrier strategies applied at VitB12 delivery are at the initial phase and aim to simplify administration, reduce costs, improve pharmacokinetics, and ameliorate the quality of patients’ lives. The safety of nanotechnologies is still under investigation and few treatments involving nanocarriers have been approved, so far. Here, we highlight the role of VitB12 in human metabolism and diseases, and the issues linked to its molecule properties, and discuss how nanocarriers can improve the therapy and supplementation of the vitamin and reduce possible side effects and limits.

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“…Spherical particles smaller than 200 nm are captured by Kupffer cells of the liver and marginal zone splenic macrophages, whereas particles higher than 200 nm are retained in the red pulp of the spleen [ 39 ]. Moreover, nanoparticles between 100–200 nm have been shown to accumulate in the BM [ 40 , 41 ]. Thus, liposomes of 100–200 nm in size have been considered as suitable for their distribution in the three infected organs (liver, spleen and BM).…”

Section: Discussionmentioning

confidence: 99%

Berberine-Loaded Liposomes for the Treatment of Leishmania infantum-Infected BALB/c Mice

et al. 2020

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Berberine (BER)—an anti-inflammatory quaternary isoquinoline alkaloid extracted from plants—has been reported to have a variety of biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded liposomes with the aim to prevent its rapid liver metabolism and improve the drug selective delivery to the infected organs in visceral leishmaniasis (VL). BER liposomes (LP-BER) displayed a mean size of 120 nm, negative Z-potential of −38 mV and loaded 6 nmol/μmol lipid. In vitro, the loading of BER in liposomes enhanced its selectivity index more than 7-fold by decreasing its cytotoxicity to macrophages. In mice, LP-BER enhanced drug accumulation in the liver and the spleen. Consequently, the liposomal delivery of the drug reduced parasite burden in the liver and spleen by three and one logarithms (99.2 and 93.5%), whereas the free drug only decreased the infection in the liver by 1-log. The organ drug concentrations—far from IC50 values— indicate that BER immunomodulatory activity or drug metabolites also contribute to the efficacy. Although LP-BER decreased 10-fold—an extremely rapid clearance of the free drug in mice—the value remains very high. Moreover, LP-BER reduced plasma triglycerides levels.

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Optimizing biodegradable nanoparticle size for tissue-specific delivery

Cited by 48 publications

References 56 publications

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients’ Lives, and Reduce Costs

Berberine-Loaded Liposomes for the Treatment of Leishmania infantum-Infected BALB/c Mice

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