Recent Innovations in the Field Of Drug Delivery

With innovators exploring new approaches to deliver drugs, the arena for drug delivery technologies continues to expand. In this article we look at some innovative drug delivery technologies which are at various phases of development.

► Halozyme’s ENHANZE® Drug Delivery Technology

Based on the recombinant human hyaluronidase PH20 enzyme (rHuPH20), Halozyme’s ENHANZE® drug delivery technology enables efficient subcutaneous delivery of co‐administered therapeutics.

The concomitant administration of rHuPH20 with partner therapies helps overcome the administration time and volume barriers associated with subcutaneous formulations - rHuPH20 degrades the glycosaminoglycan hyaluronan, which creates resistance to bulk fluid flow in the subcutaneous space and hence limits delivery of large volume drug.

Halozyme has collaborated with big hospital supply companies like Roche, Pfizer, Janssen, Baxalta, AbbVie, Eli Lilly, Bristol-Myers Squibb, Alexion and argenx. The ENHANZE drug delivery technology is approved as part of the following therapies:

• Rituxan Hycela®

• Mabthera® SC

• Hyqvia®

• Herceptin® SC

• Herceptin HylectaTM

► Suono Bio’s Ultrasound-guided Drug Delivery

Suono Bio is using low frequency sound waves as a tool for achieving more effective drug delivery.

The novel technology pairs liquid drugs with low-frequency ultrasound to create very small bubbles to push the medication directly into the gastrointestinal tract tissue. The company is targeting gastrointestinal conditions such as Crohn’s disease and ulcerative colitis that often require rectal enemas. As per animal studies, this method can deliver up to 20 times more drugs in one minute compared to the use of an enema; it also enables a shorter and less frequent use of the treatment.

Suono Bio is currently awaiting FDA approval for initiating clinical trials.

► Nemaura’s Micro-Patch platform – A Skin Drug Delivery System

Nemaura’s Pharma’s Micro-Patch platform uses a retractable microneedle to deposit solid formulations of drugs, such as biologics, under the skin. Based on this novel technology, Nemaura has developed a teriparatide microneedle product to prevent fractures in osteoporosis patients.

Teriparatide Micro-Patch comprises solid hormone coated onto a single microneedle. An aseptic process is followed for formulating the solid dose (teriparatide 20 μg) and mounting it on a single needle patch to form a shaped dose, which remains in the skin when the patch is pressed on and removed.

Poised to reduce some of the challenges of self-administration (by needle and syringe), microneedles represent a more convenient form of drug delivery. The non-invasive technology could also help to improve drug release control and absorption.

Nemaura’s microneedle patch, delivers the complete drug dose in two seconds after application. Additionally, the Micro-Patch comprises a solid dose which is stable at room temperature and hence does not require refrigeration.

► Drug Capsule to Deliver Oral Doses of Insulin

Researchers from the Massachusetts Institute of Technology (MIT) have developed a drug capsule that can be used to deliver oral doses of insulin.

The capsule contains a small needle made of compressed insulin, which is injected after the capsule reaches the stomach. The tip of the needle consists of compressed, freeze-dried insulin, while the shaft (which does not enter the stomach wall) is made from biodegradable material. The needle is attached to a compressed spring that is held in place by a disk made of sugar. When the capsule is swallowed, water in the stomach dissolves the sugar disk, releasing the spring and injecting the needle into the stomach wall.

The capsule is designed in such a way, that once it reaches the stomach, it can orient itself in a way that the needle is in contact with the lining of the stomach. This strategy will ensure that the drug is injected into the stomach wall. Once the content of the capsule is released, it can pass harmlessly through the digestive system.

In preclinical studies, the capsule was shown to deliver enough insulin to lower blood sugar to levels comparable to those produced by injections given through skin. In addition to insulin, the researchers demonstrated that the device can be used to deliver other protein-based drugs too.

The researchers have partnered with Novo Nordisk to further develop the technology and optimize the manufacturing process.

► Impel Neuropharma’s Precision Olfactory Delivery

Atypical antipsychotics, such as olanzapine, have been used for chronic and acute agitation treatment for schizophrenia and bipolar I disorder. Olanzapine can be administered orally or intramuscularly.

Oral routes of drug administration are associated with a slower-onset and often require continuous observation of the medicated patient until adequate symptom resolution. For acute agitation episodes, the intramuscular form of olanzapine is preferred over oral treatments due to a shorter time to reach maximum concentration (Tmax). However, the intramuscular route is invasive, requires a hospital setting, and poses challenges if the patient is uncooperative.

Impel NeuroPharma is developing INP105, a drug-device combination product consisting of a novel olanzapine powder formulation for upper nasal cavity administration. Impel is using precision olfactory delivery (POD) technology for developing INP105. The technology is designed to deliver olanzapine to the richly-vascularized upper nasal cavity. The novel technology is being developed to provide rapid and consistent relief of acute agitation, without excessively sedating the patient.

► Puretech’s Milk-Derived Exosome Technology

Exosomes are extracellular vesicles which play a key role in intercellular communication and the transport of macromolecules between cells and tissues. As exosomes can deliver molecular signals to recipient cells and also carry unique markers of the parental cell, they have been viewed as a promising substrate for noninvasive diagnostics and targeted drug delivery.

Due to the superior tolerability over the variety of synthetic polymers, exosomes derived from mammalian cells are an attractive tool for the administration of a variety of drug such as nucleic acids. However, most sources of mammalian exosomes lack stability under the harsh physiologic conditions of the gastrointestinal tract.  PureTech’s milk-derived exosomes is specifically designed to accomplish the task of oral transport of complex biological molecules.

PureTech licensed the exosome technology from 3P Biotechnologies. The milk exosomes helps maintain the integrity of packaged nucleic acids and proteins during transit through the gastrointestinal tract.

Milk exosomes may prove to be a promising tool to resolve the long-standing challenge of oral bioavailability of macromolecules and complex small molecules. In 2018, Roche partnered with PureTech Health to develop oral antisense oligonucleotides using PureTech’s milk-derived exosome technology.

► References

Locke KW, Maneval DC, LaBarre MJ. ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20 [published correction appears in Drug Deliv. 2019 Mar 25;:1]. Drug Deliv. 2019;26(1):98–106.

ENHANZE® drug delivery technology. Halozyme. Available at:  https://www.halozyme.com/enhanze/overview/default.aspx

Teriparatide MICRO-PATCH™: A solid microneedle product nearing clinical trials. Available at: https://www.ondrugdelivery.com/teriparatide-micro-patch-solid-microneedle-product-nearing-clinical-trials/

New pill can deliver insulin. MIT News. Available at: http://news.mit.edu/2019/pill-deliver-insulin-orally-0207

Satterly K H, Gajera B, Davies, G J, et al. Development of a Precision Olfactory Delivery (POD®)-Olanzapine Drug-Device Product for Agitation. Available at: https://escholarship.org/uc/item/0gm7913k

PureTech Health exclusively licenses novel milk-derived exosome technology. Available at: https://www.exosome-rna.com/puretech-health-exclusively-licenses-novel-milk-derived-exosome-technology/

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About the Author:

Neeta Ratanghayra is a freelance medical writer, who creates quality medical content for Pharma and healthcare industries. A Master’s degree in Pharmacy and a strong passion for writing made her venture into the world of medical writing. She believes that effective content forms the media through which innovations and developments in pharma/healthcare can be communicated to the world."