A comprehensive survey of the advanced drug delivery solutions

Have you ever missed taking your medicine? You may just let it go and tell yourself to be regular henceforth. While the implications of missing a single dose of medicine may not be serious in many cases, not adhering to a strict dosing schedule may lead to serious problems in some medical conditions or diseases such as diabetes, cancer, cardiovascular and eye diseases.

Technology can be a saviour to people who cannot adhere to a dosing schedule due to a lack of skill to administer injections, conditions like dementia, or just plain reluctance. Wearable devices (wearables) and implantable devices (implants) can automatically administer the prescribed drug according to the body requirement and a pre-decided schedule. Wearables and implants help to reduce the unnecessary repeated dosing observed in conventional drug delivery systems. They release just the required quantity of drug in a controlled manner thereby acting for a longer duration and avoiding any toxic effects on the body, otherwise observed in treatments like chemotherapy. These devices have been around for a while now and can address the lack of timely drug intake. Wearable devices are worn on the body, like an insulin pump for diabetes or pharmaceutical jewellery for contraceptive purposes. Implants are placed inside the body, like a coronary stent put in an artery during angioplasty.

Abhinanda Kar, Mahima Dewani, Lisha Awasthi and Runali Patil, from the Biosciences and Bioengineering Department, Indian Institute of Technology Bombay, under the guidance of late Prof. Rinti Banerjee and Dr Nadim Ahamad, have published a comprehensive study of wearable and implantable drug delivery devices currently being explored globally. The researchers analysed the progress in wearables and implants over the past ten years, as well as the challenges in converting these technologies to clinical settings. As Dr Ahamad, corresponding author of this paper says, “The concept of many such devices is present on an experimental level from more than 15-20 years, yet they are not available clinically to the patients. Studying challenges is important to figure out what is impeding further use of these technologies.”

Material and design requirements of wearables and implants

Wearables need to be comfortable to wear for a long duration without causing allergies or reactions. They should support easy control of the drug release and be easily replaceable without needing an expert. Implants need to be accepted by the body and should not trigger an adverse immune response. They should be implantable with minimum surgical procedure. Devices implanted in the eye need to be transparent. Wearables and implants should sustain daily body movements, hold enough amount and allow controlled drug release when used for drug delivery.

Naturally-derived non-toxic and biodegradable materials such as chitosan, alginic acid, hyaluronic acid, lipids, proteins and synthetic biodegradable materials such as polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), polyanhydrides, polyvinyl alcohol are commonly used to make wearables and implants.

The shape of implants and wearables is governed by where they are going to be used. The shape and dimensions of wearables such as mouth guards, self-care textiles and pharmaceutical jewellery are custom-designed for the comfort of the specific user. Devices like microneedle patches, wound healing bandages, and insulin patches are worn on the skin, so it is not critical to have particular dimensions. The shape and design compatibility of implantable devices is very critical, especially in applications such as vascular stents. The design needs to be precise so that they are convenient to implant and seamlessly integrate with vascular tissues.

An array of drug delivery options

When drugs are administered orally or using an injection below the skin or in a vein, the drug passes through a few body parts which are not meant to be targeted. This kind of conventional drug delivery has certain problems. A patient may need repeated doses. The medicine can create toxic reactions in the body parts other than the target area for drug delivery. Implants can deliver drugs directly to the target region and organ and reduce the possibility of a toxic reaction. In case of externally accessible tumours like breast cancer, head and neck cancer or oral cancer, devices such as hydrogel-based drug-depot and drug-releasing films deliver the drug only at the tumour site for a prolonged duration. This method can minimise adverse reactions otherwise observed in conventional chemotherapy.

Wherever wearable or implantable drug-delivery devices are available for cancer treatment, implants are more useful as they offer localised high drug dosage. Many people currently use insulin pumps, injectable pens or microneedle patches for insulin delivery in the body for diabetes management. An advanced self-powered electrothermal patch delivers insulin through the skin, and it penetrates even better than microneedle patches. Implants like injectable hydrogels, porous scaffolds, externally controlled insulin pumps and membranes made up of microfibers provide practical and reliable options for controlled delivery of insulin and other anti-diabetic drugs, thus addressing the problem of erroneous and irregular dosing.

Implants in the eye administer drugs locally to a specific part of the eye. Biocompatible and non- toxic implants are tolerated well in the eye. Even if the material degrades due to physiological conditions, the residue it creates is non-toxic and washes away with tears.

Advanced wearable and implantable devices can adjust the drug release rate according to internal factors like body movement, sweat, tears, saliva and vaginal fluid, or external triggers like light, magnetic force or ultrasound. These devices are referred to as „smart‟ wearable devices. There are „smart‟ wearables and implants that can be controlled using wireless communication too. Such remotely controlled smart devices have tremendous potential in mobile healthcare, telemedicine and personalised medicine. An interesting finding related to this is a smart and multifunctional contact lens for treating diabetic retinopathy. The lens simultaneously monitors the real-time glucose level in the tear fluid of the patient, and the patient or a healthcare provider can control the drug delivery via a wireless remote device, such that the drug gets absorbed across the cornea, sclera and retina. This contact lens was tested in the eye of a diabetic rabbit. The device showed very high sensitivity compared to standard and effective invasive procedures.

Wearable technology finds use in the treatment of certain superficially located forms of skin cancers, breast cancers and oral cancer. Anti-cancer bandages, drug-releasing self-care textiles, wearable patches and devices with microneedle patches have been used to treat cancer.

Contraception is one popular area where the wearables and implants are extensively explored for painless, affordable and long-acting drug delivery. They ensure the steady and reliable release of contraceptive hormones and avoid side effects like nausea, vomiting or irregular bleeding that oral contraceptives can cause. Pharmaceutical jewellery, drug-carrying self care textiles, intravaginal rings (IVRs) are some of the prominent developments in this area. Implantable devices can also provide contraceptive protection for several years. The very popular copper T is an example.

Implants have found an important application in making coronary stents, which have revolutionised angioplasty treatment and saved millions of lives.

Challenges in making wearables and implants

Wearables can carry only a small dosage of the drug at a time, making them unsuitable for treating diseases which demand high drug dosage, for example, certain types of cancer. Generally, they are placed on the surface of the body, but body fluids like sweat, vaginal fluid, tears and saliva can detach them from the surface. Keeping them attached to the body surface is a problem that researchers need to address before we can use these devices regularly. Making a responsive and reliable device which can release the drug as per the body‟s requirement is another challenging task. Though there are some solutions to these issues, they are yet to be tested extensively in clinical settings.

Implants have their own set of challenges. An implantable device cannot be removed or replaced in the patient‟s body without a minor or major surgical procedure. The implants can be used for a longer duration if we increase the amount of the drug that they carry at a time. This requires appropriate biomaterial for making the device, and it is still a challenge to find such material. “The purpose behind this study was to summarise and highlight the latest developments in drug delivery. We also wanted to review challenges in this area. It will help to open the channel for future research and development.” says Dr Ahamad.

Due to the ease of usage, patient friendliness and appealing functionality, wearables and implants have the potential to become the crux of drug delivery technologies. The researchers say that, for wider acceptance of these technologies, further studies should focus on investigating device accuracies, long-term stability, long-term toxic effects and various psychosocial factors that need to be addressed.