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Examples of implantable drug delivery devices for pain management, infectious disease and central nervous system disorders. ND = Not disclosed.
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The oral route is a popular and convenient means of drug delivery. However, despite its advantages, it also has challenges. Many drugs are not suitable for oral delivery due to: first pass metabolism; less than ideal properties; and side-effects of treatment. Additionally, oral delivery relies heavily on patient compliance. Implantable drug deliver...
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... well as these advantages, use of a long-acting implantable drug delivery device would ensure 100% patient compliance. An overview of some examples of implantable drug delivery devices used for pain management, infectious diseases and central nervous system disorders are summarised in Table 4. ...
Citations
... 201,202 Conversely, non-biodegradable implants are typically manufactured from materials such as silicones, polyurethanes, polyacrylates, and polyethylene vinyl acetate. [203][204][205][206][207][208][209] One notable application of implants is sustainedrelease steroids, which have proven effective in reducing inflammation and managing macular edema associated with DR. These implants provide extended therapeutic effects while minimizing the risk of systemic side effects compared to systemic steroid administration. ...
In pharmaceutical research and development, novel drug delivery systems represent a significant advancement aimed at enhancing the efficacy of therapeutic agents through innovative delivery mechanisms. The primary objective of these systems is to transport therapeutic compounds to specific target sites, such as tumors and afflicted tissues, with the dual purpose of mitigating side effects and toxicity associated with the drugs while concurrently augmenting therapeutic effectiveness. Numerous innovative drug delivery strategies have been scrutinized for their applicability in the context of targeted ocular drug delivery. Diverse novel carriers, including but not limited to implants, hydrogels, metal nanoparticles, Nano-liposomes, micelles, solid lipid nanoparticles (SLN), emulsions, and biodegradable nanoparticles, have been harnessed to facilitate the controlled release of pharmaceutical agents to the retina and vitreous. These carriers offer distinct advantages, such as enhanced intraocular drug delivery, precise control over drug release kinetics, heightened stability, and superior entrapment efficiency. This comprehensive review seeks to elucidate the current strides made in the realm of carriers and their contemporary applications in treating diabetic retinopathy (DR). Furthermore, it underscores these carriers' pivotal role in achieving efficacious intraocular drug delivery. Additionally, this article explores the various administration routes, potential future advancements, and the multifaceted challenges confronting the domain of novel carriers in treating DR. In conclusion, novel formulations are introduced to surmount the challenges associated with intraocular drug delivery.
... Magnesium ion also has antibacterial properties and can inhibit bacterial growth, prevent infection, promote proliferation and differentiation of osteoblast, and accelerate the bone healing process [60,65]. Through alloying and surface treatment technologies, the degradation rate of magnesium is effectively regulated and controlled to adapt to the time scale of bone healing, and the safety and effectiveness of magnesium in clinical application are further improved [66,67]. These comprehensive advantages make the magnesium-based materials have great potential and application prospects in the treatment of osteomyelitis. ...
The treatment of osteomyelitis, a common orthopedic infection, presents a significant challenge for clinicians. The conventional approach to treating osteomyelitis involves prolonged and high-dose antibiotic therapy along with multiple surgical debridements; however, it is plagued by inadequate therapeutic efficacy and frequent re-sensitization. Therefore, the development of biomaterials possessing localized healing and antibacterial properties is imperative. In recent years, metal-based biomaterials have emerged as a hot research topic in the management of osteomyelitis due to their inherent antibacterial and bactericidal characteristics. This article provides an overview of the benefits and applications of metal-based biomaterials in treating osteomyelitis, encompassing magnesium-based, iron-based, copper-based, and noble metal–based materials as well as other metallic biomaterials. Metal-based biomaterials exhibit remarkable potential for addressing osteomyelitis owing to their broad-spectrum antibacterial properties, biodegradability, and ability to promote the proliferation of osteoblasts. Furthermore, these materials are gradually being employed in various biomedical therapies such as sonodynamic therapy, microwave dynamic therapy, photodynamic therapy immunotherapy, and multimodal therapy for effective treatment while circumventing the limitations associated with traditional antibiotic approaches. Metal-based biomaterials hold promising prospects for managing osteomyelitis effectively. Further research should focus on exploring solutions pertaining to challenges related to drug resistance, responsible drug release, and impact on mechanical properties of matrices induced by drugs, to facilitate clinical application of metal-based biomaterials in treating osteomyelitis.
Graphical Abstract
... For the preparation of IDDSs, both biodegradable and nonbiodegradable polymers have been used (Stewart et al., 2018). Nevertheless, non-biodegradable polymers are less popular since surgical removal is necessary or they accumulate in the body after use (Dash and Cudworth II, 1998). ...
... The release kinetics in systems using swelling, osmotic pressure, or passive diffusion are influenced by factors such as the solubility and diffusion coefficient of the drug in the polymer, the drug load, and the in vivo degradation rate of the polymer. These mechanisms are essential for achieving controlled and sustained drug release in implantable delivery systems (Stewart et al., 2018). ...
... Implantable drug delivery systems (IDDS) have a wide range of clinical applications, including the treatment of chronic diseases, pain management, cancer therapy, and contraception. These devices offer several advantages over conventional drug administration methods, such as improving patient compliance, reducing side effects, and enhancing clinical outcomes (Stewart et al., 2018). Table 3 provides examples of commercially available IDDSs, classified by type, materials, therapeutic uses, and action durations. ...
In recent years, implantable drug delivery systems (IDDSs) have undergone significant advancements because they offer many advantages to patients and health care professionals. Miniaturization has reduced the size of these devices, making them less invasive and easier to implant. Remote control provides more precise medication delivery and dosage. Biodegradable implants are an additional advancement in implantable drug delivery systems that eliminate the need for surgical removal. Smart implants can monitor a patient’s condition and adjust their drug doses. Long-acting implants also provide sustained drug delivery for months or even years, eliminating the need for regular medication dosing, and wireless power and data transmission technology enables the use of devices that are more comfortable and less invasive. These innovations have enhanced patient outcomes by enabling more precise administration, sustained drug delivery, and improved health care monitoring. With continued research and development, it is anticipated that IDDSs will become more effective and provide patients with improved health outcomes. This review categorizes and discusses the benefits and limitations of recent novel IDDSs for their potential therapeutic use.
... These devices were prepared with biocompatible and biodegradable polymers: PLA and PCL [61]. Therefore, these implants will not need to be removed after cargo release. ...
The current investigation aims to address the limitations of conventional cancer therapy by developing an advanced, long-term drug delivery system using biocompatible Rose Bengal (RB)-loaded polyvinyl alcohol (PVA) matrices incorporated into 3D printed polycaprolactone (PCL) and polylactic acid (PLA) implants. The anticancer drug RB’s high solubility and low lipophilicity require frequent and painful administration to the tumour site, limiting its clinical application. In this study, RB was encapsulated in a PVA (RB@PVA) matrix to overcome these challenges and achieve a localised and sustained drug release system within a biodegradable implant designed to be implanted near the tumour site. The RB@PVA matrix demonstrated an RB loading efficiency of 77.34 ± 1.53%, with complete RB release within 30 min. However, when integrated into implants, the system provided a sustained RB release of 75.84 ± 8.75% over 90 days. Cytotoxicity assays on PC-3 prostate cancer cells indicated an IC50 value of 1.19 µM for RB@PVA compared to 2.49 µM for free RB, effectively inhibiting cancer cell proliferation. This innovative drug delivery system, which incorporates a polymer matrix within an implantable device, represents a significant advancement in the sustained release of hydrosoluble drugs. It holds promise for reducing the frequency of drug administration, thereby improving patient compliance and translating experimental research into practical therapeutic applications.
... [14] Various methods exist for gradually releasing antibiotics, such as coating the implant with specific materials to impede biofilm formation or embedding antibiotics within porous structures in the implant itself. [15] Previous research has explored passive drug release via coating [16] or drug dispensation within the implant chamber [17] based on diffusion. However, traditional chemical coating approaches, involving antibiotics and antibacterial peptides applied to modified titanium surfaces, exhibit a rapid decline in antibacterial potency over time. ...
Enabling minimally invasive and precise control of liquid release in dental implants is crucial for therapeutic functions such as delivering antibiotics to prevent biofilm formation, infusing stem cells to promote osseointegration, and administering other biomedicines. However, achieving controllable liquid cargo release in dental implants remains challenging due to the lack of wireless and miniaturized fluidic control mechanisms. Here wireless miniature pumps and valves that allow remote activation of liquid cargo delivery in dental implants, actuated and controlled by external magnetic fields (<65 mT), are reported. A magnet‐screw mechanism in a fluidic channel to function as a piston pump, alongside a flexible magnetic valve designed to open and close the fluidic channel, is proposed. The mechanisms are showcased by storing and releasing of liquid up to 52 µL in a dental implant. The liquid cargos are delivered directly to the implant–bone interface, a region traditionally difficult to access. On‐demand liquid delivery is further showed by a metal implant inside both dental phantoms and porcine jawbones. The mechanisms are promising for controllable liquid release after implant placement with minimal invasion, paving the way for implantable devices that enable long‐term and targeted delivery of therapeutic agents in various bioengineering applications.
... Despite being the preferred route for drug administration, it presents challenges for the management of chronic conditions, as the patient needs to adhere to the treatment [11,12]. A potential alternative to solve this issue is long-acting drug delivery systems [13][14][15][16][17]. These systems are typically injected or implanted into the patient, providing sustained drug dosage after a single administration [13][14][15][16][17][18]. ...
... A potential alternative to solve this issue is long-acting drug delivery systems [13][14][15][16][17]. These systems are typically injected or implanted into the patient, providing sustained drug dosage after a single administration [13][14][15][16][17][18]. Long-acting drug delivery systems have been prepared in a wide range of shapes and materials including solid subcutaneous implants [14,19,20], injectable suspensions [21,22] or in situ forming implants/gels [23][24][25][26]. ...
To overcome the challenges of the blood-brain barrier for drug delivery to the central nervous system (CNS), intranasal implants were developed to improve the management of CNS conditions, such as schizophrenia. In the present work, we developed and characterised a drug-containing implant consisting of two parts: a core layer made from risperidone (RIS) and water-soluble polymers, including poly(vinylpyrrolidone) (PVP) and poly (ethylene glycol) (PEG), and a coating layer made of poly(caprolactone) (PCL) membrane. The obtained implants , where the core layer contained 75 % w/w risperidone, were characterised using several techniques: scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR). Moreover, the in vitro release profile of RIS was studied, showing that the PCL membrane could extend the release of RIS from 2 days up to 100 days. The in vitro release profile of the PCL-coated implant exhibited a linear release over the first 10 days, followed by a slower release rate that reached another linear phase up to 40 days. Subsequently, the drug release rates progressively slowed down. Finally, the results of in vitro biocompatibility studies indicated that the intranasal implants were biocompatible and non-cytotoxic. These findings suggest that the implants prepared in this work have the potential to provide long-acting drug delivery for targeting the brain.
... These products, which contain substances such as lactic and glycolic acids which are found naturally in the body, are safely metabolized or excreted and pose no harm. They meet the standard specifications for nontoxicity [16]. These components offer advantages such as biodegradability, elimination of the need for additional surgeries for removal, and supporting tissue regeneration. ...
This study evaluated the bone incorporation process of a screw-shaped internal fixation device made of poly (L-lactide-coD , L-lactide) (PLDLLA). Thirty-two male Wistar rats received 32 fixation devices (2 mm × 6 mm) randomly assigned to either the right or left tibia and one implant in each animal. After 7, 14, 28, and 42 days, the rats were euthanized and the specimens were subjected to microtomographic computed tomography (microCT) and histomorphometric analyses to evaluate bone interface contact (BIC%) and new bone formation (NBF%) in cortical and cancellous bone areas. The animals euthanized on days 28 and 42 were treated with calcein and alizarin red, and confocal LASER microscopy was performed to determine the mineral apposition rate (MAR). Micro-CT revealed a higher percentage of bone volume (p < 0.006), trabecular separation (p < 0.001), and BIC in the cortical (p < 0.001) and cancellous (p = 0.003) areas at 28 and 42 days than at 7 and 14 days. The cortical NBF at 42 days was greater than that at 7 and 14 days (p = 0.022). No statistically significant differences were observed in cancellous NBF or MAR at 28 and 42 days. Based on these results, it can be seen that the PLDLLA internal fixation device is biocompatible and allows new bone formation around the screw thread.
... 110 If a nonbiodegradable material is used for an implant and if removal is necessary, surgical removal of the implants/devices would be employed to remove the implants. 111 Thus, biodegradable materials are highly sought after for medical and biomedical applications. ...
A UV‐ and thermo‐responsive polyurethane‐acrylate prepolymer was synthesized from palm olein (POo) via a non‐isocyanate route. The process included epoxidation of POo, carbonation of epoxidized palm olein (EPOo) into polycyclic carbonate in a solvent‐free and mild condition (100°C, 1 atm), followed by reacting with ethylene diamine and acrylic acid. The chemical structure of the non‐isocyanate polyurethane‐acrylate (NIPUA) prepolymer was elucidated by ¹H and ¹³C nuclear magnetic resonance (NMR) and Fourier transform‐infrared spectroscopy (FTIR), while weight average molecular weight of NIPUA was determined by gel permeation chromatography (GPC). The NIPUA (0–20 wt%) was incorporated with thermoplastic elastomer (TPE) as a plasticizer and cured under UV light and thermal stimulations. The cured NIPUA/TPE films were characterized by FTIR, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and tensile strength test. Under UV and thermal stimulations, the NIPUA/TPE demonstrated enhanced tensile properties (elongation at break >1280%, Young's modulus ~25 MPa), thermal properties (lower Tg), lower water contact angle, and shortened curing time as compared with the blank TPE. The 20 wt% NIPUA/TPE films exhibited susceptibility to enzymatic biodegradation and noncytotoxic to HEK 293 cells in vitro, demonstrated it's potential as a UV‐ and thermo‐responsive plasticizer for TPE in manufacturing of medical devices.
... Subcutaneous microdisks are becoming a popular form of parenteral sustained release dosage as they avoid the need for more invasive surgeries. Biodegradable polymers are preferred for the manufacture of these devices as they can be metabolised and excreted by the body, therefore avoiding the need for surgical removal at the end of the treatment [29]. One of these commonly used formulation materials is carboxymethylcellulose, a natural linear polysaccharide with excellent biocompatibility and biodegradability widely used in drug delivery processes [30] approved by the FDA for human pharmacological use ("Code of federal regulations": FDA department of health and human services, Title 21, Volume 5, Chapter 1, Subchapter D, Drugs for human use (21CFR310.545)," ...
Saethre-Chotzen syndrome (SCS) is one of the most prevalent craniosynostosis, caused by a loss-of-function mutation in the TWIST-1 gene, with current treatment options relying on major invasive transcranial surgery. TWIST-1 haploinsufficient osteogenic progenitor cells exhibit increased osteogenic differentiation potential due to an upregulation of the transmembrane tyrosine kinase receptor, C-ROS-1, a TWIST-1 target gene known to promote bone formation. The present study assessed the efficacy of suppressing C-ROS-1 activity using a known chemical inhibitor to C-ROS-1, crizotinib, to halt premature coronal suture fusion in a preclinical mouse model of SCS. Crizotinib (1 μM, 2 μM, or 4 μM) was administered locally over the calvaria of Twist‐1del/+ heterozygous mice prior to coronal suture fusion using either a nonresorbable collagen sponge (quick drug release) or a resorbable sodium carboxymethylcellulose microdisk (slow sustained release). Coronal suture fusion rates and bone parameters were determined by μCT imaging and histomorphometric analysis of calvaria postcoronal suture fusion. Results demonstrated a dose-dependent increase in the efficacy of crizotinib to maintain coronal suture patency, with no adverse effects to brain, kidney, liver, and spleen tissue, or blood cell parameters. Moreover, crizotinib delivered on microdisks resulted in a greater efficacy at a lower concentration to reduce bone formation at the coronal suture sites compared to sponges. However, the bone inhibitory effects were found to be diminished by over time following cessation of treatment. Our findings lay the foundation for the development of a pharmacological nonsurgical, targeted approach to temporarily maintain open coronal sutures in SCS patients. This study could potentially be used to develop similar therapeutic strategies to treat different syndromic craniosynostosis conditions caused by known genetic mutations.
... At present, a tendency to achieve proper administration is to obtain long-acting drug delivery systems, which are able of providing sustained and/or local drug delivery, thus contributing to improve the success of the bone replacement and patient compliance [8][9][10]. In this sense, hydrogels are three-dimensional crosslinked hydrophilic polymeric networks that are capable of absorbing and retaining significant amounts of water or biological fluids without being dissolved themselves [11,12]. ...
Bone-tissue replacement surgeries usually need medication to mitigate implant rejections or21 prevent local infections. In this study, a modulated and targeted tetracycline (TC) loaded gelatine type A22 hydrogel is release from Ti foams as a proof of concept for an innovative and intelligent drug release system.23 The drugs are released in a localized and controlled manner. The Ti foams fabricated by the space holder24 technique were surface modified by two different techniques of surface modification, i.e., thermal oxidation25 and acid etching, to assess their influence on TC release. The characterization carried out after the surface26 modification indicated that samples modified with acid etching have produced a rougher surface, increasing27 the diameter of pores (from 500 microns to 700 microns, approximately) due to coalescence of pores. The28 increase of pore roughness has demonstrated the delaying of the TC release due to the greater adhesion29 between the surface roughness and the hydrogel. In addition, the increase of pore size improves the30 possibility to infiltrate high amount of drug-loaded biocompatible hydrogel. Opposite, oxidized surface31 samples have generated a rutile type TiO2 layer that, because of its hydrophilic nature facilitate the32 degradation of the hydrogel, and consequently, the TC release from the Ti foams. Therefore, both methods33 show opposite behaviour, available to increase (acid etching) or decrease (thermal oxidation) the TC release34 thanks to the different kinetic degradation of hydrogel, as a potential way for drug-release from metallic35 implants. Thus, while acid-etched samples showed maximum TC release value of 35 wt.%, after 120 min,36 the oxidized samples surpassed the 40 % of TC release after same 120 min of release time treatment.
