Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations

Ballacchino, Giulia; Weaver, Edward; Mathew, Essyrose; Dorati, Rossella; Genta, Ida; Conti, Bice; Lamprou, Dimitrios A.

doi:10.3390/ijms22158064

Cited by 48 publications

(35 citation statements)

References 42 publications

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“…Comparing the morphometric results of TEM and DLS analysis, it can be stated that liposome bilayer thickness is in keeping with what is reported in the literature, taking into consideration that molecular weight of building compounds is 10 2 [ 18 ]. This result corroborates what is reported in the literature [ 19 , 20 , 21 ]. The liposomes were loaded with two different proteins, namely myoglobin and bovine serum albumin.…”

Section: Discussionsupporting

confidence: 93%

Liposome Formulation and In Vitro Testing in Non-Physiological Conditions Addressed to Ex Vivo Kidney Perfusion

Pisani

Chiesa

Dorati

et al. 2022

IJMS

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This work focuses on formulating liposomes to be used in isolated kidney dynamic machine perfusion in hypothermic conditions as drug delivery systems to improve preservation of transplantable organs. The need mainly arises from use of kidneys from marginal donors for transplantation that are more exposed to ischemic/reperfusion injury compared to those from standard donors. Two liposome preparation techniques, thin film hydration and microfluidic techniques, are explored for formulating liposomes loaded with two model proteins, myoglobin and bovine serum albumin. The protein-loaded liposomes are characterized for their size by DLS and morphology by TEM. Protein releases from the liposomes are tested in PERF-GEN perfusion fluid, 4 °C, and compared to the in vitro protein release in PBS, 37 °C. Fluorescent liposome uptake is analyzed by fluorescent microscope in vitro on epithelial tubular renal cell cultures and ex vivo on isolated pig kidney in hypothermic perfusion conditions. The results show that microfluidics are a superior technique for obtaining reproducible spherical liposomes with suitable size below 200 nm. Protein encapsulation efficiency is affected by its molecular weight and isoelectric point. Lowering incubation temperature slows down the proteins release; the perfusion fluid significantly affects the release of proteins sensitive to ionic media (such as BSA). Liposomes are taken up by epithelial tubular renal cells in two hours’ incubation time.

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Section: Discussionsupporting

confidence: 93%

Liposome Formulation and In Vitro Testing in Non-Physiological Conditions Addressed to Ex Vivo Kidney Perfusion

Pisani

Chiesa

Dorati

et al. 2022

IJMS

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“…In this work, channels of 1 mm in diameter were fabricated; however, narrower channels are possible by PDMS, up to 100-200 µm [44]. A diameter of 1 mm was enough to result in adequate mixing, leading to nanoparticles of around 100 nm, which is 3-fold smaller than previous works [45]. Similar particle sizes (100-200 nm) were obtained previously for liposomes when 3D printed microfluidic chips made of polylactic acid using an FDM printer with 600 µm channel diameter were used [46].…”

Section: Discussionmentioning

confidence: 91%

Engineering 3D Printed Microfluidic Chips for the Fabrication of Nanomedicines

et al. 2021

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Currently, there is an unmet need to manufacture nanomedicines in a continuous and controlled manner. Three-dimensional (3D) printed microfluidic chips are an alternative to conventional PDMS chips as they can be easily designed and manufactured to allow for customized designs that are able to reproducibly manufacture nanomedicines at an affordable cost. The manufacturing of microfluidic chips using existing 3D printing technologies remains very challenging because of the intricate geometry of the channels. Here, we demonstrate the manufacture and characterization of nifedipine (NFD) polymeric nanoparticles based on Eudragit L-100 using 3D printed microfluidic chips with 1 mm diameter channels produced with two 3D printing techniques that are widely available, stereolithography (SLA) and fuse deposition modeling (FDM). Fabricated polymeric nanoparticles showed good encapsulation efficiencies and particle sizes in the range of 50–100 nm. SLA chips possessed better channel resolution and smoother channel surfaces, leading to smaller particle sizes similar to those obtained by conventional manufacturing methods based on solvent evaporation, while SLA manufactured nanoparticles showed a minimal burst effect in acid media compared to nanoparticles fabricated with FDM chips. Three-dimensional printed microfluidic chips are a novel and easily amenable cost-effective strategy to allow for customization of the design process for continuous manufacture of nanomedicines under controlled conditions, enabling easy scale-up and reducing nanomedicine development times, while maintaining high-quality standards.

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“…3D printing is a modern technology that has been used recently to fabricate microfluidic devices. Compared to other mentioned microfluidic fabrication systems, 3D printing is low-priced, time-saving, and multiple-purpose [146].…”

Section: Microfluidicsmentioning

confidence: 99%

Microfluidics Technology for the Design and Formulation of Nanomedicines

et al. 2021

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In conventional drug administration, drug molecules cross multiple biological barriers, distribute randomly in the tissues, and can release insufficient concentrations at the desired pathological site. Controlling the delivery of the molecules can increase the concentration of the drug in the desired location, leading to improved efficacy, and reducing the unwanted effects of the molecules under investigation. Nanoparticles (NPs), have shown a distinctive potential in targeting drugs due to their unique properties, such as large surface area and quantum properties. A variety of NPs have been used over the years for the encapsulation of different drugs and biologics, acting as drug carriers, including lipid-based and polymeric NPs. Applying NP platforms in medicines significantly improves the disease diagnosis and therapy. Several conventional methods have been used for the manufacturing of drug loaded NPs, with conventional manufacturing methods having several limitations, leading to multiple drawbacks, including NPs with large particle size and broad size distribution (high polydispersity index), besides the unreproducible formulation and high batch-to-batch variability. Therefore, new methods such as microfluidics (MFs) need to be investigated more thoroughly. MFs, is a novel manufacturing method that uses microchannels to produce a size-controlled and monodispersed NP formulation. In this review, different formulation methods of polymeric and lipid-based NPs will be discussed, emphasizing the different manufacturing methods and their advantages and limitations and how microfluidics has the capacity to overcome these limitations and improve the role of NPs as an effective drug delivery system.

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Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations

Cited by 48 publications

References 42 publications

Liposome Formulation and In Vitro Testing in Non-Physiological Conditions Addressed to Ex Vivo Kidney Perfusion

Liposome Formulation and In Vitro Testing in Non-Physiological Conditions Addressed to Ex Vivo Kidney Perfusion

Engineering 3D Printed Microfluidic Chips for the Fabrication of Nanomedicines

Microfluidics Technology for the Design and Formulation of Nanomedicines

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