Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing

Stewart, Sarah A.; Domínguez-Robles, Juan; McIlorum, Victoria J; Mancuso, Elena; Lamprou, Dimitrios A.; Donnelly, Ryan F.; Larrañeta, Eneko

doi:10.3390/pharmaceutics12020105

Cited by 116 publications

(60 citation statements)

References 51 publications

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“…Single-screw HME was used to produce the PLA filament for the implant manufacture in combination with the PVA filament. As described previously by Stewart et al, 23 PLA pellets were added to a filament extruder (3Deveo, Utretch, The Netherlands) at an extrusion speed of 5 rpm and a filament fan speed of 70%. The temperature was controlled between 170 and 190 °C.…”

Section: Methodsmentioning

confidence: 99%

Poly(caprolactone)-Based Coatings on 3D-Printed Biodegradable Implants: A Novel Strategy to Prolong Delivery of Hydrophilic Drugs

et al. 2020

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Implantable devices are versatile and promising drug delivery systems, and their advantages are well established. Of these advantages, long-acting drug delivery is perhaps the most valuable. Hydrophilic compounds are particularly difficult to deliver for prolonged times. This work investigates the use of poly(caprolactone) (PCL)-based implant coatings as a novel strategy to prolong the delivery of hydrophilic compounds from implantable devices that have been prepared by additive manufacturing (AM). Hollow implants were prepared from poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA) using fused filament fabrication (FFF) AM and subsequently coated in a PCL-based coating. Coatings were prepared by solution-casting mixtures of differing molecular weights of PCL and poly(ethylene glycol) (PEG). Increasing the proportion of low-molecular-weight PCL up to 60% in the formulations decreased the crystallinity by over 20%, melting temperature by over 4 °C, and water contact angle by over 40°, resulting in an increased degradation rate when compared to pure high-molecular-weight PCL. Addition of 30% PEG to the formulation increased the porosity of the formulation by over 50% when compared to an equivalent PCL-only formulation. These implants demonstrated in vitro release rates for hydrophilic model compounds (methylene blue and ibuprofen sodium) ranging from 0.01 to 34.09 mg/day, depending on the drug used. The versatility of the devices produced in this work and the range of release rates achievable show great potential. Implants could be specifically developed in order to match the specific release rate required for a number of drugs for a wide range of conditions.

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Section: Methodsmentioning

confidence: 99%

Poly(caprolactone)-Based Coatings on 3D-Printed Biodegradable Implants: A Novel Strategy to Prolong Delivery of Hydrophilic Drugs

et al. 2020

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“…This technology can be used to fabricate pharmaceutical formulations in different sizes and shapes using a variety of materials with customized drug concentrations and release profiles that cannot be produced using conventional mass production methods in the pharmaceutical industry [ 8 ]. Different types of 3D printers using inkjet printing [ 9 ], stereolithography (SLA) [ 10 ], selective laser sintering (SLS) [ 11 ], fused deposition modeling [ 12 ], and extrusion-based pressure-assisted micro syringes [ 13 ] have been used to develop various types of drug delivery systems and novel devices such as transdermal patches [ 14 ], intrauterine and sub-cutaneous devices [ 15 , 16 ], and biodegradable implants [ 17 ]. Recently, Dumpa et al developed a gastro-retentive floating pulsatile drug delivery system where the investigator enclosed a theophylline tablet prepared by direct compression into a floating shell, exploiting the 3D printing technique (hot-melt extrusion-paired fused-deposition modeling) for the treatment of chronic asthma [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

et al. 2020

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The use of 3D printing techniques to control drug release has flourished in the past decade, although there is no generic solution that can be applied to the full range of drugs or solid dosage forms. The present study provides a new concept, using the 3D printing technique to print a coating system in the form of shells with various designs to control/modify drug release in immediate-release tablets. A coating system of cellulose acetate in the form of an encapsulating shell was printed through extrusion-based 3D printing technology, where an immediate-release propranolol HCl tablet was placed inside to achieve a sustained drug release profile. The current work investigated the influence of shell composition by using different excipients and also by exploring the impact of shell size on the drug release from the encapsulated tablet. Three-dimensional printed shells with different ratios of rate-controlling polymer (cellulose acetate) and pore-forming agent (D-mannitol) showed the ability to control the amount and the rate of propranolol HCl release from the encapsulated tablet model. The shell-print approach also showed that space/gap available for drug dissolution between the shell wall and the enclosed tablet significantly influenced the release of propranolol HCl. The modified release profile of propranolol HCl achieved through enclosing the tablet in a 3D printed controlled-release shell followed Korsmeyer–Peppas kinetics with non-Fickian diffusion. This approach could be utilized to tailor the release profile of a Biopharmaceutics Classification System (BCS) class I drug tablet (characterized by high solubility and high permeability) to improve patient compliance and promote personalized medicine.

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“…Among all the applications, 3DP has been recently used for the manufacture of a range of drug delivery systems and medical devices. 4,6,7 Despite these recent developments, 3DP is not a new technique as the first patent describing this technology was filled in the late 80s. 8 However, the field of 3DP experienced a huge increase in popularity during the past 15 years due to the ''democratization'' of this technology.…”

Section: Additive Manufacturing For Health Care Professionalsmentioning

confidence: 99%

Additive Manufacturing Can Assist in the Fight Against COVID-19 and Other Pandemics and Impact on the Global Supply Chain

Larrañeta

Domínguez-Robles

Lamprou

2020

3D Printing and Additive Manufacturing

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105

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The high demand on medical devices and personal protective equipment (PPE) during the COVID-19 crisis left millions of health care professionals unprotected in the middle of this situation, as governments around the world were not prepared for such pandemic. The three-dimensional printing (3DP) community, from universities to 3DP enthusiasts with printers at home, was there to support hospitals from day 1 on this demand by providing PPE and other medical supplies (e.g., face shields and valves for respiratory machines). This editorial covers the importance of 3DP in the fight against COVID-19 and how this can be used to tackle potential pandemics and support the supply chain.

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Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing

Cited by 116 publications

References 51 publications

Poly(caprolactone)-Based Coatings on 3D-Printed Biodegradable Implants: A Novel Strategy to Prolong Delivery of Hydrophilic Drugs

Poly(caprolactone)-Based Coatings on 3D-Printed Biodegradable Implants: A Novel Strategy to Prolong Delivery of Hydrophilic Drugs

Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

Additive Manufacturing Can Assist in the Fight Against COVID-19 and Other Pandemics and Impact on the Global Supply Chain

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