Development of 3D-Printed Layered PLGA Films for Drug Delivery and Evaluation of Drug Release Behaviors

Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.

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3D Printed Microheater Sensor-Integrated, Drug-Encapsulated Microneedle Patch System for Pain Management

10.1101/788877 ◽

2019 ◽

Author(s):

Mengtian Yin ◽

Li Xiao ◽

Qingchang Liu ◽

Sung-Yun Kwon ◽

Yi Zhang ◽

...

Keyword(s):

Drug Delivery ◽

Pain Management ◽

Drug Release ◽

Elevated Temperatures ◽

Performance Assessments ◽

Wearable Electronics ◽

Multiwalled Carbon ◽

3D Printed ◽

Microneedle Patch ◽

Subsequent Diffusion

AbstractMicroneedle patch device has been widely utilized for transdermal drug delivery in pain management, but is challenged by accurate control of drug release and subsequent diffusion to human body. The recent emerging wearable electronics that could be integrated with microneedle devices offers a facile approach to address such a challenge. Here a 3D printed microheater integrated drug-encapsulated microneedle patch system for drug delivery is presented. The ink solution comprised of polydimethylsiloxane (PDMS) and multiwalled carbon nanotubes (MWCNTs) with mass concentration of up to 45% is prepared and used to print crack-free stretchable microheaters on substrates with a broad range of materials and geometric curves. The adhesion strength of printed microheater on microneedle patch in elevated temperatures are measured to evaluate their integration performance. Assessments of encapsulated drug release into rat’s skin are confirmed by examining degradation of microneedles, skin morphologies, and released fluorescent signals. Results and demonstrations established here creates a new opportunity for developing sensor controlled smart microneedle patch systems by integrating with wearable electronics, potentially useful in clinic and biomedical research.

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A 3D printed drug delivery implant formed from a dynamic supramolecular polyurethane formulation

Polymer Chemistry ◽

10.1039/d0py00068j ◽

2020 ◽

Vol 11 (20) ◽

pp. 3453-3464 ◽

Cited By ~ 1

Author(s):

S. Salimi ◽

Y. Wu ◽

M. I. Evangelista Barreiros ◽

A. A. Natfji ◽

S. Khaled ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Effective Drug ◽

Drug Eluting ◽

3D Printed

Prototype drug eluting implants have been 3D printed using a supramolecular polyurethane-PEG formulation. The implants are capable of releasing a pharmaceutical active with effective drug release over a period of up to 8.5 months.

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Oral drug delivery systems using core–shell structure additive manufacturing technologies: a proof-of-concept study

Journal of Pharmacy and Pharmacology ◽

10.1093/jpp/rgaa037 ◽

2021 ◽

Author(s):

Jiaxiang Zhang ◽

Pengchong Xu ◽

Anh Q Vo ◽

Michael A Repka

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Drug Release ◽

Water Soluble ◽

Oral Drug ◽

Core Shell ◽

Fluid Medium ◽

Fused Deposition ◽

Enhanced Solubility ◽

3D Printed

Abstract Objectives The aim of this study was to couple fused deposition modelling 3D printing with melt extrusion technology to produce core–shell-structured controlled-release tablets with dual-mechanism drug-release performance in a simulated intestinal fluid medium. Coupling abovementioned technologies for personalized drug delivery can improve access to complex dosage formulations at a reasonable cost. Compared with traditional pharmaceutical manufacturing, this should facilitate the following: (1) the ability to manipulate drug release by adjusting structures, (2) enhanced solubility and bioavailability of poorly water-soluble drugs and (3) on-demand production of more complex structured dosages for personalized treatment. Methods Acetaminophen was the model drug and the extrusion process was evaluated by a series of physicochemical characterizations. The geometries, morphologies, and in vitro drug-release performances were compared between directly compressed and 3D-printed tablets. Key findings Initially, 3D-printed tablets released acetaminophen more rapidly than directly compressed tablets. Drug release became constant and steady after a pre-determined time. Thus, rapid effectiveness was ensured by an initially fast acetaminophen release and an extended therapeutic effect was achieved by stabilizing drug release. Conclusions The favourable drug-release profiles of 3D-printed tablets demonstrated the advantage of coupling HME with 3D printing technology to produce personalized dosage formulations.

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The Improvement of Paclitaxel Cytotoxicity using Nanocellulose based Nature Resources

Journal of Engineering and Scientific Research ◽

10.23960/jesr.v1i1.3 ◽

2019 ◽

Vol 1 (1) ◽

pp. 7

Author(s):

R Nahrowi ◽

A Setiawan ◽

Noviany Noviany ◽

I Sukmana ◽

S D Yuwono

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Natural Resources ◽

Cell Viability ◽

Cancer Cells ◽

Drug Delivery System ◽

Target Cell ◽

Mitotic Cycle ◽

Potential Sources ◽

Local Accumulation

Paclitaxel is one of the cancer drugs that often used. These drug kills cancer cells byinhibiting mitotic cycle. The efficiency of paclitaxel is increased by the use ofnanomaterials as a carrier of paclitaxel. Nanomaterials can enhance encapsulationefficiency, improve the drug release to the target cell following nanomaterialdegradation, and improve local accumulation of drug in the cell through endocytosisreceptor. Nanomaterial that often used forencapsulation of paclitaxel is a polymerderived from natural resources such as cellulose. The advantages of cellulose as acarrier of paclitaxel are nontoxic, biodegradable, and very abundant from varioussources. One of the potential sources of cellulose for drug delivery system is cassavabaggase.Keywords: Paclitaxel, encapsulation, cell viability, nanocellulose

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Acyclovir Loaded Solid Lipid Nanoparticle Based Cream: A Novel Drug Delivery System

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v7i1.8917 ◽

2017 ◽

Vol 7 (1) ◽

Author(s):

EL- Assal I. A. ◽

Retnowati .

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Antiviral Agent ◽

Study Drug ◽

Particle Size Analysis ◽

Stability Study ◽

Size Analysis ◽

Solid Lipid ◽

Dermal Delivery

Objective of the present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir. Also study vitro and vivo drug delivery. Methods: Drug loaded SLNs (ACV-SLNs) were prepared by high pressure homogenization of aqueous surfactant solutions containing the drug-loaded lipids in the melted or in the solid state with formula optimization study (Different lipid concentration, drug loaded, homogenization / stirring speed and compritol 888ATO: drug ratio). ACV - SLN incorporated in cream base. The pH was evaluated and rheological study. Drug release was evaluated and compared with simple cream- drug, ACV – SLN with compritol 888ATO and marketed cream. The potential of SLN as the carrier for dermal delivery was studied. Results: Particle size analysis of SLNs prove small, smooth, spherical shape particle ranged from 150 to 200 nm for unloaded and from 330 to 444 nm for ACV loaded particles. The EE% for optimal formula is 72% with suitable pH for skin application. Rheological behavior is shear thinning and thixotropic. Release study proved controlled drug release for SLNs especially in formula containing compritol88 ATO. Stability study emphasized an insignificant change in SLNs properties over 6 month. In-vivo study showed significantly higher accumulation of ACV in stratum corneum, dermal layer, and receptor compartment compared with blank skin. Conclusion: AVC-loaded SLNs might be beneficial in controlling drug release, stable and improving dermal delivery of antiviral agent(s).

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Development and Evaluation of Floating Pulsatile Drug Delivery System Using Meloxicam

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v7i04.10647 ◽

2017 ◽

Vol 7 (04) ◽

Author(s):

ShirishaG. Suddala ◽

S. K. Sahoo ◽

M. R. Yamsani

Keyword(s):

Rheumatoid Arthritis ◽

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Lag Time ◽

Oral Dosage ◽

Lag Phase ◽

Pulsatile Drug Delivery

Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro drug release studies, water uptake and erosion studies, floating behaviour and in vivo radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.

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Formulation, Development and Characterization of Floating Beads of Diltiazem Hydrochloride

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v6i1.8883 ◽

2016 ◽

Vol 6 (1) ◽

Author(s):

Anamika Saxena Saxena ◽

Santosh Kitawat ◽

Kalpesh Gaur ◽

Virendra Singh

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Entrapment Efficiency ◽

Repeated Administration ◽

Alginate Beads ◽

Delivery Systems ◽

Sem Analysis ◽

Formulation Development

The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and nontoxic for a prolonged period. Various attempts have been made to develop gastroretentive delivery systems such as high density system, swelling, floating system. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application. Background of the research: Diltiazem HCL (DTZ), has short biological half life of 3-4 h, requires rather high frequency of administration. Due to repeated administration there may be chances of patient incompliance and toxicity problems. Objective: The objective of study was to develop sustained release alginate beads of DTZ for reduction in dosing frequency, high bioavailability and better patient compliance. Methodology: Five formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared. Alginate beads were prepared by ionotropic external gelation technique using CaCl2 as cross linking agent. Prepared beads were evaluated for % yield, entrapment efficiency, swelling index in 0.1N HCL, drug release study and SEM analysis. In order to improve %EE and drug release, LMP and sunflower oil were used as copolymers along with sodium alginate.

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Development of Solid Lipid Nanoparticles of Lamivudine for Brain Targeting

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v1i1.8837 ◽

2009 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Pravin Patil ◽

Anil Sharma ◽

Subhash Dadarwal ◽

Vijay Sharma

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Solid Lipid Nanoparticles ◽

Rotation Speed ◽

Lipid Nanoparticles ◽

Brain Targeting ◽

Brain Penetration ◽

Solid Lipid ◽

Diffusion Technique

The objective of present investigation was to enhance brain penetration of Lamivudine, one of the most widely used drugs for the treatment of AIDS. This was achieved through incorporating the drug into solid lipid nanoparticles (SLN) prepared by using emulsion solvent diffusion technique. The formulations were characterized for surface morphology, size and size distribution, percent drug entrapment and drug release. The optimum rotation speed, resulting into better drug entrapment and percent yield, was in the range of 1000-1250 r/min. In vitro cumulative % drug release from optimized SLN formulation was found 40-50 % in PBS (pH-7.4) and SGF (pH-1.2) respectively for 10 h. After 24 h more than 65 % of the drug was released from all formulations in both mediums meeting the requirement for drug delivery for prolong period of time.

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Biodegradable 3D Printed Polymer Microneedles for Transdermal Drug Delivery

10.26434/chemrxiv.5851950.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Michael A. Luzuriaga ◽

Danielle R. Berry ◽

John C. Reagan ◽

Ronald A. Smaldone ◽

Jeremiah J. Gassensmith

Keyword(s):

Drug Delivery ◽

3D Printing ◽

Transdermal Drug Delivery ◽

Fused Deposition Modeling ◽

Fused Deposition ◽

Modeling Software ◽

Deposition Modeling ◽

3D Printed ◽

Microfabrication Technique ◽

Mechanical Strengths

Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1 – 55 µm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.

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