Development of a gastroretentive delivery system for acyclovir by 3D printing technology and its in vivo pharmacokinetic evaluation in Beagle dogs

Background: 3D printed pharmaceutical products are revolutionizing the pharmaceutical industry as a prospective mean to achieve a personalized method of treatments acquired to the specially designed need of each patient. It will depend upon age, weight, concomitants, pharmacogenetics and pharmacokinetic profile of the patient and thus transforming the current pharmaceutical market as a potential alternative to conventional medicine. 3D printing technology is getting more consideration in new medicine formulation development as a modern and better alternative to control many challenges associated with conventional medicinal products. There are many advantages of 3D printed medicines which create tremendous opportunities for improving the acceptance, accuracy and effectiveness of these medicines. In 2015, United State Food and Drug Administration has approved the first 3D printed tablet (Spritam®) and had shown the emerging importance of this technology. Methods: This review article summarizes as how in-depth knowledge of drugs and their manufacturing processes can assist to manage different strategies for various 3D printing methods. The principal goal of this review is to provide a brief introduction about the present techniques employed in tech -medicine evolution from conventional to a novel drug delivery system. Results: It is evidenced that through its unparalleled advantages of high-throughput, versatility, automation, precise spatial control and fabrication of hierarchical structures, the implementation of 3D printing for the expansion and delivery of controlled drugs acts as a pivotal role. Conclusion: 3D printing technology has an extraordinary ability to provide elasticity in the manufacturing and designing of composite products that can be utilized in programmable and personalized medicine. Personalized medicine helps in improving drug safety and minimizes side effects such as toxicity to individual human being which is associated with unsuitable drug dose.

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In Vitro and In Vivo Bioequivalence Study of 3D-Printed Instant-Dissolving Levetiracetam Tablets and Subsequent Personalized Dosing for Chinese Children Based on Physiological Pharmacokinetic Modeling

Pharmaceutics ◽

10.3390/pharmaceutics14010020 ◽

2021 ◽

Vol 14 (1) ◽

pp. 20

Author(s):

Xianfu Li ◽

En Liang ◽

Xiaoxuan Hong ◽

Xiaolu Han ◽

Conghui Li ◽

...

Keyword(s):

3D Printing ◽

Pbpk Model ◽

Dose Range ◽

Chinese Children ◽

Pbpk Modeling ◽

Printing Technology ◽

3D Printing Technology ◽

Pbpk Models ◽

3D Printed

Recently, the development of Binder Jet 3D printing technology has promoted the research and application of personalized formulations, which are especially useful for children’s medications. Additionally, physiological pharmacokinetic (PBPK) modeling can be used to guide drug development and drug dose selection. Multiple technologies can be used in combination to increase the safety and effectiveness of drug administration. In this study, we performed in vivo pharmacokinetic experiments in dogs with preprepared 3D-printed levetiracetam instant-dissolving tablets (LEV-IDTs). Bioequivalence analysis showed that the tablets were bioequivalent to commercially available preparations (Spritam®) for dogs. Additionally, we evaluated the bioequivalence of 3D-printed LEV-IDTs with Spritam® by a population-based simulation based on the established PBPK model of levetiracetam for Chinese adults. Finally, we established a PBPK model of oral levetiracetam in Chinese children by combining the physiological parameters of children, and we simulated the PK (pharmacokinetics) curves of Chinese children aged 4 and 6 years that were administered the drug to provide precise guidance on adjusting the dose according to the effective dose range of the drug. Briefly, utilizing both Binder jet 3D printing technology and PBPK models is a promising route for personalized drug delivery with various age groups.

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Noninvasive in vivo 3D bioprinting

Science Advances ◽

10.1126/sciadv.aba7406 ◽

2020 ◽

Vol 6 (23) ◽

pp. eaba7406 ◽

Cited By ~ 10

Author(s):

Yuwen Chen ◽

Jiumeng Zhang ◽

Xuan Liu ◽

Shuai Wang ◽

Jie Tao ◽

...

Keyword(s):

3D Printing ◽

Near Infrared ◽

Clinical Medicine ◽

Application Site ◽

3D Bioprinting ◽

Printing Technology ◽

3D Printing Technology ◽

Tissue Constructs

Three-dimensional (3D) printing technology has great potential in advancing clinical medicine. Currently, the in vivo application strategies for 3D-printed macroscale products are limited to surgical implantation or in situ 3D printing at the exposed trauma, both requiring exposure of the application site. Here, we show a digital near-infrared (NIR) photopolymerization (DNP)–based 3D printing technology that enables the noninvasive in vivo 3D bioprinting of tissue constructs. In this technology, the NIR is modulated into customized pattern by a digital micromirror device, and dynamically projected for spatially inducing the polymerization of monomer solutions. By ex vivo irradiation with the patterned NIR, the subcutaneously injected bioink can be noninvasively printed into customized tissue constructs in situ. Without surgery implantation, a personalized ear-like tissue constructs with chondrification and a muscle tissue repairable cell-laden conformal scaffold were obtained in vivo. This work provides a proof of concept of noninvasive in vivo 3D bioprinting.

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Rapid manufacturing of micro-drilling devices using FFF-type 3D printing technology

Scientific Reports ◽

10.1038/s41598-021-91149-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sangyeun Park ◽

Byeongjo Ko ◽

Heewon Lee ◽

Hongyun So

Keyword(s):

3D Printing ◽

Three Dimensional ◽

Dynamics Simulation ◽

Drilling Depth ◽

Printing Technology ◽

3D Printing Technology ◽

Drilling Performance ◽

Micro Drilling ◽

Fluidic Resistance

AbstractMicro-drilling devices with different blade shapes were fabricated with a rapid and facile manufacturing process using three-dimensional (3D) printing technology. The 3D-printed casting mold was utilized to customize the continuous shape of the blades without the need for expensive manufacturing tools. A computational fluid dynamics simulation was performed to estimate the pressure differences (fluidic resistance) around each rotating device in a flowing stream. Three types of blades (i.e., 45°, 0°, and helical type) were manufactured and compared to a device without blades (i.e., plain type). As a result, the device with the 45° blades exhibited the best drilling performance. At a rotational speed of 1000 rpm, the average drilling depth of the device with the 45° blades to penetrate artificial thrombus for 90 s was 3.64 mm, which was ~ 2.4 times longer than that of helical blades (1.51 mm). This study demonstrates the feasibility of using 3D printing to fabricate microscale drilling devices with sharp blades for various applications, such as in vivo microsurgery and clogged water supply tube maintenance.

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Vascularized Bone Regeneration Accelerated by 3D-Printed Nanosilicate-Functionalized Polycaprolactone Scaffold

Regenerative Biomaterials ◽

10.1093/rb/rbab061 ◽

2021 ◽

Author(s):

Xiongcheng Xu ◽

Long Xiao ◽

Yanmei Xu ◽

Jin Zhuo ◽

Xue Yang ◽

...

Keyword(s):

3D Printing ◽

Bone Regeneration ◽

Bone Repair ◽

Cytokine Secretion ◽

Printing Technology ◽

3D Printing Technology ◽

3D Printed ◽

Vascularized Bone

Abstract Critical oral-maxillofacial bone defects, damaged by trauma and tumors, not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct. Personalized biomaterials customized by 3D printing technology have the potential to match oral-maxillofacial bone repair and regeneration requirements. Laponite nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity. Herein, porous nanosilicate-functionalized polycaprolactone (PCL/LAP) was fabricated by 3D printing technology, and its bioactivities in bone regeneration were investigated in vitro and in vivo. In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the viability of BMSCs. PCL/LAP functioned to stimulate osteogenic differentiation of BMSCs at the mRNA and protein levels and elevated angiogenic gene expression and cytokine secretion. Moreover, BMSCs cultured on PCL/LAP promoted the angiogenesis potential of endothelial cells by angiogenic cytokine secretion. Then, PCL/LAP scaffolds were implanted into the calvarial defect model. Toxicological safety of PCL/LAP was confirmed, and significant enhancement of vascularized bone formation was observed. Taken together, 3D-printed PCL/LAP scaffolds with brilliant osteogenesis to enhance bone regeneration could be envisaged as an outstanding bone substitute for a promising change in oral-maxillofacial bone defect reconstruction.

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3D Printing in Personalized Drug Delivery

Current Pharmaceutical Design ◽

10.2174/1381612825666190215122208 ◽

2019 ◽

Vol 24 (42) ◽

pp. 5062-5071 ◽

Cited By ~ 9

Author(s):

Afsana ◽

Vineet Jain ◽

Nafis Haider ◽

Keerti Jain

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Personalized Medicine ◽

Drug Delivery System ◽

Delivery System ◽

Dosage Forms ◽

Printing Technology ◽

3D Printing Technology ◽

Fused Deposition ◽

Personalized Medicines

Background: Personalized medicines are becoming more popular as they enable the use of patient’s genomics and hence help in better drug design with fewer side effects. In fact, several doses can be combined into one dosage form which suits the patient’s demography. 3 Dimensional (3D) printing technology for personalized medicine is a modern day treatment method based on genomics of patient. Methods: 3D printing technology uses digitally controlled devices for formulating API and excipients in a layer by layer pattern for developing a suitable personalized drug delivery system as per the need of patient. It includes various techniques like inkjet printing, fused deposition modelling which can further be classified into continuous inkjet system and drop on demand. In order to formulate such dosage forms, scientists have used various polymers to enhance their acceptance as well as therapeutic efficacy. Polymers like polyvinyl alcohol, poly (lactic acid) (PLA), poly (caprolactone) (PCL) etc can be used during manufacturing. Results: Varying number of dosage forms can be produced using 3D printing technology including immediate release tablets, pulsatile release tablets, and transdermal dosage forms etc. The 3D printing technology can be explored successfully to develop personalized medicines which could play a vital role in the treatment of lifethreatening diseases. Particularly, for patients taking multiple medicines, 3D printing method could be explored to design a single dosage in which various drugs can be incorporated. Further 3D printing based personalized drug delivery system could also be investigated in chemotherapy of cancer patients with the added advantage of the reduction in adverse effects. Conclusion: In this article, we have reviewed 3D printing technology and its uses in personalized medicine. Further, we also discussed the different techniques and materials used in drug delivery based on 3D printing along with various applications of the technology.

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Three-Dimensional-Printed Poly-L-Lactic Acid Scaffolds with Different Pore Sizes Influence Periosteal Distraction Osteogenesis of a Rabbit Skull

BioMed Research International ◽

10.1155/2020/7381391 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Danyang Zhao ◽

Wenbo Jiang ◽

Yu Wang ◽

Chuandong Wang ◽

Xiaoling Zhang ◽

...

Keyword(s):

Lactic Acid ◽

3D Printing ◽

Distraction Osteogenesis ◽

Animal Experiments ◽

Three Dimensional ◽

Printing Technology ◽

Pore Sizes ◽

3D Printing Technology

The repair of bone defects is a big challenge in reconstructive surgery. Periosteal distraction osteogenesis (PDO), as a promising technique used for bone regeneration, forms a space between the periosteum and bone cortex to regenerate the new bone merely by distracting the periosteum. In order to investigate the influence of distractor framework on the PDO, we utilized three-dimensional (3D) printing technology to fabricate three kinds of poly-L-lactic acid (PLLA) scaffolds with different pore sizes in this study. The in vitro experiments showed that the customized PLLA scaffolds had different-sized microchannels with low toxicity, good biocompatibility, and enough mechanical strength. Then, we built up an in vivo bioreactor under the skull periosteum of New Zealand white rabbits. The distractors with different pore sizes all could satisfy the demand of periosteal distraction in the animal experiments. After 8 weeks of consolidation period, the quality and quantity of the newly formed bone were improved with the increasing pore sizes of the distractors. Moreover, the newly formed bone also displayed an increasing degree of vascularization. In conclusion, 3D printing technology could promote the innovation of PDO devices and fabricate optimized scaffolds with appropriate pore sizes, shapes, and structures. It would help us regenerate more functional tissue-engineered bone and provide new ideas for further clinical application of the PDO technique.

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