Oral delivery of biologics using drug-device combinations

Abstract

Orally administered devices could enable the systemic uptake of biologic therapeutics by engineering around the physiological barriers present in the gastrointestinal (GI) tract. Such devices aim to shield cargo from degradative enzymes and increase the diffusion rate of medication through the GI mucosa. In order to achieve clinical relevance, these designs must significantly increase systemic drug bioavailability, deliver a clinically relevant dose and remain safe when taken frequently. Such an achievement stands to reduce our dependence on needle injections, potentially increasing patient adherence and reducing needle-associated complications. Here we discuss the physical and chemical constraints imposed by the gastrointestinal organs and use these to develop a set of boundary conditions on oral device designs for the delivery of macromolecules. We critically examine how device size affects the rate of intestinal obstruction and hinders the loading capacity of poorly soluble protein drugs. We then discuss how current orally administered devices could solve the problem of tissue permeation and conclude that these physical methods stand to provide an efficacious alternative to the classic hypodermic needle.

Oral Delivery of Biologics for Precision Medicine

“…The stomach on the other side, has been classically regarded as transit region where drugs could be retained and degraded, due to the low pH, presence of gastric enzymes, and thickest mucus layer of the GIT. [7,11] However, other features such as the fact of being the first place for drug delivery, and the fast epithelial regeneration, [12,13] have led to reconsider its potential. Emerging gastric delivery technologies leveraging from these properties will be commented later.…”

“…[6] Essentially, biological drugs including peptides, monoclonal antibodies, and nucleic acids offer a much higher specificity and potency than small molecule drugs. [7,8] However, these properties are derived from their large and complex macromolecular structure, which also hampers the preservation of their bioactivity as well as their interaction with biological barriers. [8,9] As a consequence, these macromolecules need to be administered via injection, while drug delivery technologies are being designed to allow for their administration through alternative routes.…”

An ingestible self-orienting system for oral delivery of macromolecules

“…The discovery and purification of insulin transformed our capacity to effectively treat diabetes mellitus (3), yet health care providers delay insulin initiation an average of 7.7 years and instead prescribe less effective oral medications (4). Orally bioavailable biologic dosage forms may allow health care providers to prescribe these effective medications more quickly, yet the development of such systems poses challenges (5). Orally administered therapeutic proteins must navigate extremes of pH, protease-rich environments, thick mucus layers, and cellular tight junctions before achieving systemic bioavailability (6).…”

Recent advances in oral delivery of biologics: nanomedicine and physical modes of delivery

“…Oral drug delivery devices resemble more conventional oral solid dosage forms (e.g. capsules), but carry small electronic and/or mechanical elements [101]. According to MarketsandMarkets TM , 'smart pills' market is expected to reach $8.98 billion in sales by 2024 [102].…”