1. Introduction
A drug delivery system refers to the method and route by which a drug is delivered to the site where it will act in the body to show its treatment efficacy. Effective drug delivery requires a multidisciplinary approach and a comprehensive understanding of the drug’s properties and the targeted site. However, the lack of targeted delivery limits its efficacy and bioavailability [
1]. A collaborative effort between pharmacologists, biologists, chemists, and engineers is required to optimise drug delivery and disease detection [
2]. Drug delivery systems comprise various technologies and strategies that are formulated with the objective of conveying therapeutic agents to their targeted site of action within the human body. These systems employ diverse strategies and pathways of administration that are customised to suit the distinctive requirements of the medication and the targeted therapeutic region. Oral delivery, through tablets, capsules, or liquids, is the most common and convenient method. Injectable delivery allows for precise dosage control and rapid absorption when administered subcutaneously, intramuscularly, intravenously, or intra-arterially. Topical delivery involves applying medications to the skin or mucous membranes, while inhalation delivery is through aerosols, gases, or powders for direct respiratory system delivery. Transdermal delivery uses patches or devices for consistent drug release. Implantable delivery involves surgical placement for long-term release. Targeted delivery systems accumulate drugs at specific sites, such as tumours or the brain. Smart drug delivery is an innovative approach that amalgamates advanced devices, state-of-the-art sensors, and sophisticated software into drug delivery systems, aiming to optimise drug efficacy, safety, and patient compliance [
3]. Such systems are designed explicitly to release medication automatically based on a patient’s health status, thus mitigating human error and ensuring optimal dosing at the right time [
4]. It enables personalised medicine by monitoring the patient’s health status, allowing for tailored drug dosage and release. Systems can improve medication compliance and reduce the burden of managing complex regimens, a challenge for many patients [
5].
The objective of this review article is to analyse and evaluate the various methodologies and technological advancements in IoT-based drug delivery systems This paper deals in great depth with how IoT can be used to monitor patients’ critical illnesses and deliver drugs, including a comparison of modern technology to traditional drug delivery methods. It also outlines the problems with technology, drug delivery, and protocol design using IoT, as well as the solutions to the problems and the direction of future study. A comprehensive literature search was conducted using databases such as PubMed, Scopus, and IEEE Xplore using relevant keywords such as “IoT drug delivery”, “wearable devices”, “implantable devices”, “micro and nano-technologies”, and “remote patient care” to identify relevant studies published between 2013 and 2023.
Inclusion and Exclusion Criteria: Inclusion criteria were applied to select studies that focused on IoT technology in drug delivery, encompassing wearable devices, implantable devices, and ingestible and remote IoT-based drug delivery approaches. Studies that were not directly related to IoT-based drug delivery or those that did not provide substantial information on their methodology were excluded.
Data Extraction: Relevant information was extracted from the selected studies, including study design, device description, methodologies employed, key findings, limitations, and implications.
Analysis of data: The extracted data were analysed to identify common methodologies used in the development and implementation of IoT-based drug delivery systems. Key themes, technological innovations, challenges, and gaps in the existing literature were identified.
Comparative Analysis: A comparison and the contrast between the methodologies used in different studies, highlighting the strengths and limitations of each approach, was performed along with identifying the patterns, trends, and emerging techniques in IoT-based drug delivery systems.
The paper is organised as follows:
Section 1 describes conventional and smart drug delivery systems.
Section 2 highlights IoT, healthcare IoT, and its components. The recent applications of smart drug delivery devices are listed and described in detail in
Section 3. The related work and its comparative analysis are described in
Section 4.
Section 5 deals with security issues faced by WSN in healthcare and their prevention. The regulatory aspect of smart drug delivery devices in healthcare is discussed in
Section 6.
Section 7 depicts the issues and challenges in IoT networks and their solutions mentioned in
Section 8.
Section 9 lists the future prospects of smart drug delivery, and
Section 10 concludes the paper.
3. Applications of Smart Drug Delivery Devices
IoT-based drug delivery systems are becoming increasingly popular in the healthcare sector due to their potential to enhance the accuracy, efficiency, and effectiveness of drug delivery. In smart drug delivery systems, various algorithms are involved to analyse data, make intelligent decisions, and optimise treatment. Closed-loop control algorithms are used in systems such as closed-loop insulin delivery for diabetes management, where real-time sensor data are continuously monitored and analysed to determine the appropriate drug dosage or delivery rate. Pharmacokinetic and pharmacodynamic algorithms utilise mathematical models to optimise dosing regimens and predict drug responses based on factors such as drug absorption, distribution, metabolism, and excretion. Machine learning algorithms can analyse large datasets to identify patterns or correlations that inform drug dosing decisions and optimise treatment outcomes. These algorithms enable personalised dosing recommendations, adaptive dosing adjustments, and real-time alerts, enhancing the effectiveness and safety of drug delivery systems [
14]. Smart drug delivery systems hold significant potential in improving medication compliance and reducing the burden of complex regimens. IoT-based systems provide unique advantages for smart drug delivery, leveraging their connectivity and seamless data exchange capabilities. With real-time monitoring and data analytics, IoT sensors continuously track drug delivery parameters, patient responses, and environmental factors, enabling prompt intervention and optimised treatment protocols [
3]. Remote access and connectivity allow healthcare providers to remotely monitor patient progress, making them particularly valuable for chronic disease management and telemedicine services. Enhanced patient engagement through mobile apps, wearables, and interactive interfaces empowers patients to actively participate in their treatment, leading to improved self-management and treatment outcomes [
13]. The scalability and interoperability of IoT infrastructure enable seamless integration with existing healthcare systems, allowing smart drug delivery systems to adapt to evolving needs. Predictive maintenance and data-driven insights optimise system reliability, resource allocation, and workflow efficiency. The classification of IoT-based drug delivery systems is shown in
Figure 5.
3.1. Wearable Smart Drug Delivery Devices
IoT-based wearable drug delivery devices are innovative solutions for healthcare, leveraging technology to improve delivery accuracy and efficiency. Worn on the body, like a patch or wristband, health devices track vital indicators and administer medication based on collected data. The devices aid medication adherence for patients with chronic conditions, reducing the risk of adverse events occurring.
3.1.1. Smart Insulin Pens
Smart insulin pens use IoT technology to track and manage insulin delivery for diabetes patients. They transmit dosage and schedule information wirelessly, helping providers monitor treatment. Smart insulin pens provide precise dosing based on blood sugar levels, time, and activity, preventing health complications. Smart insulin pens can help diabetics manage their condition by providing insightful data about their insulin usage [
15]. By tracking doses and blood sugar levels, users can detect patterns and receive tailored recommendations for treatment and lifestyle modifications with the associated mobile app. The branded smart insulin pens that are available commercially, and their limitations, are listed in
Table 1.
3.1.2. Wearable Infusion Pumps
Wearable infusion pumps deliver medications through a catheter under the skin. They are portable, discreet, and programmed to administer precise doses at specific times, providing continuous medication throughout the day. Wearable infusion pumps offer convenient and mobile delivery of medication while minimising infection risk by avoiding disturbance to the infusion site. Wearable infusion pumps offer precise dosing and can adjust medication based on real-time glucose levels for personalised treatment. The wearable infusion pumps for smart drug delivery, and their limitations, are listed in
Table 2.
3.1.3. Smart Inhalers
Smart inhalers are a type of wearable smart drug delivery device that assists individuals with breathing disorders such as asthma and COPD to better manage their symptoms. These devices can monitor a patient’s inhaler usage, provide reminders to take medication, and track medication adherence over time. Some smart inhalers are also able to measure lung function and provide feedback to patients and their healthcare providers. The information gathered by intelligent inhalers can be utilised to enhance treatment strategies, enhance patient results, and decrease healthcare expenditure. The smart inhalation devices for drug delivery, and their limitations, are listed in
Table 3.
3.1.4. Smart Auto-Injectors
Smart auto-injectors are programmable medical devices that are designed to automatically inject a specific dose of medication. They are also equipped with IoT technology which enables them to connect to other devices or networks and share data in real-time. The IoT-enabled smart auto-injectors are used to administer various types of medication, such as insulin, epinephrine, and other types of drugs. They can be pre-programmed to deliver medication at a specific time or when certain physiological parameters are detected, such as glucose levels in the case of diabetes patients.
Table 4 shows some examples of smart auto-injectors for drug delivery.
3.2. Implatable Smart Drug Delivery Devices
IoT (internet of things)-based implantable drug delivery devices are a growing trend in the healthcare industry, offering new and innovative solutions for drug delivery. These devices leverage IoT technology to provide real-time monitoring and control of drug delivery, improving the accuracy and efficiency of the delivery process.
3.2.1. Implantable Infusion Pumps
These devices are implantable pumps that can deliver drugs, such as pain medications or chemotherapy, directly to the site of action. The pumps can be controlled wirelessly using a smartphone or other device, allowing healthcare providers to adjust the delivery rate as needed.
Implantable sensor-based infusion pumps are medical devices that are surgically implanted into the body to deliver precise doses of medication, such as insulin for the treatment of diabetes or pain medication for the management of chronic pain. These devices are equipped with sensors that can monitor the patient’s physiological parameters and adjust the delivery of medication accordingly. Some examples of implantable sensor-based infusion pumps are given in
Table 5.
3.2.2. Implantable Drug-Eluting Stents
These are stents that are implanted in blood vessels to deliver drugs, such as anti-inflammatory or anti-proliferative agents, directly to the site of action. The stents can be controlled wirelessly using a smartphone or other device, allowing healthcare providers to adjust the delivery rate as needed. A list of some examples of implantable drug-eluting stents is given in
Table 6.
3.3. Ingestible Smart Drug Delivery Devices
IoT-based ingestible smart drug delivery devices are another growing trend in the healthcare industry. These devices leverage IoT technology to provide real-time monitoring and control of drug delivery, improving the accuracy and efficiency of the delivery process. Some examples of IoT-based ingestible smart drug delivery devices are given in
Table 7.
4. Research Survey for Exploring the Role of IoT in Revolutionising Healthcare
IoT technology improves drug delivery by allowing real-time monitoring, personalised dosing, and remote patient care. Studies have explored IoT drug delivery for chronic disease, cancer, and pain management, with the literature examining technical, clinical, and regulatory challenges.
In research conducted in 2020 [
43], a laboratory syringe pump was developed as an open-source solution using Arduino UNO and an LCD keypad shield for easy device interaction and setting changes without a computer connection. The device infused fluids and refilled syringes. Analysing a 10 mL syringe showed a systematic error of 0.1% and a random error of 3 L for dispensed volumes of 1–5 mL. In another study [
44], a new wearable and disposable glucose monitoring device that used sweat for non-invasive measurement, which included pH, temperature, and humidity measurements for real-time glucose level correction, contained temperature-responsive nanoparticles in hyaluronic acid hydrogel microneedles. This innovation offered non-invasive diabetes mellitus treatment by monitoring glucose through sweat analysis.
Bi-hormonal systems aim to prevent low blood sugar events and maintain glucose within the targeted range by delivering both glucagon or amylin and insulin; these were tested in [
45]. To enhance islet transplantation, encapsulation strategies were used that promote angiogenesis, oxygen delivery, and immune protection, which eliminate immunosuppression and enhance long-term survival and function. A new implant delivers drugs precisely using micro- and nano-technologies; a CMOS SoC device combines wireless control, actuation, and drug delivery [
46]. This device can be implanted via minimally invasive surgery to treat cancer and heart attacks. Another new drug delivery approach, using a wireless micropump with acoustofluidic technology [
47], which was compact, wirelessly controlled, and integrated with technology, miniaturised sensors, and electronics that could create on-demand drug delivery systems. New soft and thin neural probes (MICROFLUIDIC) that injected drugs precisely into deep brain tissue wirelessly and with high control over time and location were shown in research carried out in 2015 [
48]. Using 3D printing, an electrochemical pump with an expandable Parylene C micro-bellows membrane and precise microneedles (100 m diameter, 300 m long) for drug delivery was constructed by Moussi K. in 2019 [
49]; it could deliver the drug in 10 s using wireless power up to a 10 mm distance. In a recent study [
50], miniaturised heaters with resonant frequencies of 30–100 MHz were equipped with hydrogel, and the temperature was elevated by up to 20 °C, shrinking the hydrogel by 40%. This showed a frequency-controlled release with an active range of 2 MHz. A 2013 [
51] drug delivery system injected antiepileptic drugs at the onset of an electrographic seizure to enhance seizure control. The system included a seizure detector, preamplifier, wireless control module, and micropump unit, with emphasis on the micropump prototype. The results indicated that the micropump was precise, low-power, and suitable for implantable use in responsive drug delivery. Researchers also developed a drug delivery system within the IoT that offers real-time medication administration for seizure control [
52]. The system used a valveless micropump, powered by electromagnetics and made of flexible polydimethylsiloxane, for precise drug delivery. The authors in [
53] introduced an innovative cancer therapy using an IoT-based micropumping device for wireless reconfiguration. This implantable device stored anticancer drugs in refillable reservoirs and allowed remote control and adjustment of drug administration. In vitro tests showed that the system delivered anticancer drugs accurately, inhibiting breast cancer cells by over 71%.
An IoT-based anaesthesia drug control system for monitoring and controlling anaesthesia drugs for patients was designed in [
54]. The system detects pulse rate and temperature to adjust anaesthesia. It uses NodeMCU for control. Ubidots cloud allowed medical professionals to monitor patient data via IoT. It showed an efficient solution for anaesthesia control. IV drug administration is effective, but manual setup lacks accuracy and monitoring. Radioactive scan chamber safety concerns led to a clinical survey in 2021 [
55] to find an improved device for intravenous drips. This study proposes an IoT-based device to address air embolism and blood backflow and improve drug administration for neonates and paediatrics. The device solves manual IV drip control and offers real-time monitoring.
Wireless controllers are now essential in healthcare, with researchers exploring advanced medical devices for efficient medication delivery. In research work [
56], a smartphone-controlled iontophoretic drug delivery device with a hardware module and mobile app for drug delivery control was developed. It features a safety mechanism to detect loose leads and stop drug delivery. The device’s performance was tested in an in vitro drug release investigation, yielding promising results for emulsion gel-based drug delivery. India’s healthcare sector is important to its economy, but high costs are a concern. AIDD proposes using IoT and ML for an improved insulin delivery system for comatose patients [
57]. Multiple ML models were used to predict insulin doses for diabetic patients remotely, eliminating the need for physical assistance. A remote system with interconnected devices that delivers drugs and prognosis was designed in [
58]. This system enabled monitoring of patients’ vital signs, collecting sensor data, and regulating drug release via an implantable pump. Rigorous testing confirmed the system’s effectiveness in remote medical care. In recent times, due to COVID-19, COPD patients in hospitals struggled to receive proper drug injections and monitoring. A system was created with medical devices and IoT technology to provide the necessary oxygen and vital signs monitoring [
59]. The system had two sections: one monitored the drip rate and fluid volume using an IR sensor and photodiode, and the other controlled the nebulization speed and duration with an Arduino Nano and MOSFET. This system improved COPD patients’ quality of life through better medical care. The authors in [
60] proposed an IoT and AI system with fuzzy learning to regulate anaesthesia during surgery. Adaptable and robust to surgical disturbances, a system using sliding mode control, type II fuzzy systems, and artificial neurons was used to regulate anaesthesia drug infusion and adjust the bispectral index. It also allowed for remote drug infusion adjustments. The automated temperature controller (AMTC) was developed in 2021 [
61] for synthesising NiO and CuO nanoparticles. The device created dexamethasone-loaded nanomicelles for testing transcorneal penetration. It had the potential for other controlled thermal reactions, providing a compact solution.
In 2015 [
62], an implanted micropump device using electrolysis, EI sensors, and wireless technology for drug delivery was formulated. This system was tested successfully for controlled infusion rate, sensed dosage in simulated brain tissue, and estimated coil separation and off-centre. RFID tags with helical antennas and drug compartments for tracking drug dosage in real-time were created, with two prototypes being tested to monitor drug dosage changes in vitro [
63]. The results showed a sensitivity of 1.27 L/MHz for transdermal delivery and 2.76 L/MHz for implanted delivery. Another new approach for anticancer drug delivery to brain tumours with a biodegradable patch and wireless system is described in [
64]. Promising results were found in mouse and large animal models, with tumour volume suppression and improved survival rates, indicating the potential for treating brain tumours in humans. The best way to treat medical conditions is with localised and controlled drug release using a wireless implant that is biodegradable and does not require surgical extraction; one such implant was studied in 2015 [
65]. The system’s efficacy and biocompatibility were proven through in vitro and in vivo studies. Wearable technology measures vital signs, leading to disease control. Closed-loop systems use wearables to deliver drugs for complete control. This text focuses on closed-loop systems and transdermal delivery technologies enabled by digital wearables [
66]. A miniaturised dental patch system was developed [
67] to monitor the microenvironment and control fluoride treatment for early prevention and management of tooth decay caused by oral biomes. The system utilises near-field communication for wireless data transmission with smart devices attached to the teeth.
In a study performed in 2021 [
68], researchers created a wireless, self-powered, and smart wound dressing for infection treatment and supervision. Its flexible electronics detect infestations, deliver medication, and allow for independent monitoring and treatment. This experiment shows potential for closed-loop biomedical systems. An implantable drug delivery device (SID) for neurological emergencies that integrates wirelessly with wearables monitoring EEG signals was designed [
69], which, when tested in animals, showed that using the SID reduced brain damage and improved survival rates. In [
70], wearable devices delivered drugs via the skin with electrical control. The drug is administered through a paper electrode with polypyrrole and sodium salicylate. Using different potentials, this device controlled drug release dose and rate, making it ideal for closed-loop delivery and the detection of various illnesses. In another study [
71], an electro-drug system for the GI tract with a capsule containing drugs, sensors, wireless capabilities, and motors was developed. Twenty healthy volunteers underwent two observational studies to evaluate the safety and functionality of the ingested capsule. In another study, 99 mTc was expelled remotely from the capsule and tracked by scintigraphy. The results showed that the capsule was safe and well tolerated, with successful transmission of temperature and pH data in 96.5% of cases. The 99 mTc was successfully removed remotely in 9 of 10 subjects, and its location correlated with scintigraphy based on pH. The wireless system [
72] remotely powered the implanted device, controlling the dose rate with voltage and resistance adjustments. Proof-of-concept for the system’s feasibility and controllability was demonstrated with liquid and solid drugs. The results showed consistent flow rates and steady dose release, even with a solid drug substitute. A new approach [
73] integrated sensors with drug delivery devices using carbon ink embedded in PDMS membranes for accurate volume monitoring. The device delivers 7 L of drug solution with a 6.5% accuracy.
Contemporary research has advanced multiple potential methodologies for drug delivery that encompass diverse approaches, such as wearable and disposable glucose monitoring devices, bi-hormonal systems, encapsulation strategies, implantable devices exploiting micro- and nano-technologies, pliable and slender neural probes, 3D printing, frequency-controlled release, valveless micropumps, and iontophoretic drug delivery devices, which could potentially be employed for anaesthesia regulation, intravenous drips, insulin delivery, remote medical care, chronic obstructive pulmonary disease patient monitoring, etc. The utilisation of wireless controllers, cloud computing, and machine learning algorithms has facilitated the expansion of remote patient monitoring and drug administration. Existing studies and their limitations are listed in
Table 8.
8. Solution of Challenges
IoT-based drug delivery presents a number of challenges that must be overcome in order to fully realise its potential. One of the most critical challenges is ensuring the security and privacy of patient data. This requires the development of robust security measures, including encryption, authentication, and access control, to safeguard patient information from unauthorised access or data breaches. Interoperability and standardisation of IoT devices and platforms are also necessary to improve compatibility and facilitate seamless communication between devices, ultimately reducing costs and improving performance.
Another challenge is compliance with regulatory frameworks to ensure patient safety and build trust in the technology. This includes adhering to various regulations and standards such as HIPAA, GDPR, and ISO 13485, which provide guidelines for data privacy, security, and quality management. Additionally, the accuracy and reliability of IoT devices must be ensured through testing and validation processes to ensure the technology can be relied upon to deliver effective and safe healthcare.
To manage the deployment and maintenance of IoT devices, healthcare organisations must invest in adequate staffing and training. This can help to ensure that the devices are managed properly and patient data remains secure and confidential. Ethical and social considerations should also be addressed to ensure that IoT-based drug delivery systems align with the values and needs of patients, healthcare providers, and other stakeholders.
While the benefits of IoT-based drug delivery are clear, the cost of developing and implementing such systems can be a significant barrier for many healthcare organisations. To manage costs, it is crucial to adopt better approaches to cost modelling, outlining the expenses associated with hardware and software architectures, and ensuring proper cost estimation.
Connectivity and reliability are also crucial for IoT-based drug delivery systems. Designers must prioritise connectivity and testing during the early stages of development to ensure that the devices can function continuously without any failures. The use of fog computing can also help to reduce data processing delays that can occur due to the long distance between IoT sensors and data processing devices. By providing faster data processing and reducing reliance on cumbersome cloud storage, fog computing can improve the quality of service and make the IoT more useful for healthcare by allowing doctors to make better-informed decisions.