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

Abstract

Research into oral delivery of biologics has a long and rich history but has not produced technologies used in the clinic. The area has evolved in terms of strategies to promote oral biologics delivery from early chemical absorption enhancers to nanomedicine to devices. Continued activity in this area is justifiable considering the remarkable proliferation of biologics. Areas covered: The article discusses some physiological barriers to oral delivery of biologics, with a special focus on less characterized barriers such as the basement membrane. Recent progress in oral delivery of biologics via nanomedicine is subsequently covered. Finally, the emerging field of device-mediated gastrointestinal delivery of biotherapeutics is discussed. Expert opinion: Oral delivery of biologics is considered a 'panacea' in drug delivery. Almost century-old approaches of utilizing chemical absorption enhancers have not produced clinically translated technologies. Nanomedicine for oral biologics delivery has demonstrated potential, but the field is relatively new, and technologies have not progressed to the clinic. Device-mediated oral biologics delivery (e.g. ultrasound or microneedles) is in its infancy. However, this space is likely to intensify owing to advances in electronics and materials, as well as the challenges and history related to clinical translation of alternative approaches.

Engineering Biomimetic Gelatin Based Nanostructures as Synthetic Substrates for Cell Culture

“…In the field of drug delivery, while the drug barrier functions of mucus and epithelium are relatively well-characterized, the filter function of the BM is seldom studied [10][11][12]. But currently, there is a growing interest to understand the barrier function of the BM due to advances in the mucosal delivery of complex therapeutics such as macromolecules and nanomedicines [12,13]. The diffusion of macromolecules through the BM of non-keratinized oral mucosal epithelium was initially studied by Alfano et al, who observed that the BM restricts the penetration of smaller macromolecules (inulin, 5 kDa), while allowing easy passage of larger macromolecules (Dextran, 20 kDa) [14].…”

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

“…Several formulation strategies have emerged for the delivery of proteins orally ( Table 3 ). The use of protease inhibitors to dampen proteolytic enzyme activity, and permeation enhancers [ 105 , 236 , 237 ], ultrasound [ 238 , 239 ], microjet systems [ 238 , 240 ] and microneedle capsules [ 238 , 241 ] to improve drug absorption have recently been explored as techniques to maintain the bioactivity of the administered proteins as well as enhance transport through disrupted tight junctions [ 105 ]. These formulations are capable of remaining intact throughout transit and allow for drug absorption into the systemic circulation.…”

“…Patches are relatively novel systems for oral delivery of small and macromolecules with mucoadhesive properties [ 242 ]. Similar to a transdermal patch, intestinal patches are able to encapsulate and protect the desired drug while adhering to the intestinal wall [ 238 , 242 ], thus positioning the drug at the desired absorption site [ 241 ]. A patch consists of three layers: a mucoadhesive material, a drug-loaded layer and a relatively impermeable drug-protecting membrane [ 242 ].…”

“…The patches are then loaded into enteric-coated capsules, for example, which dissolve in the intestine to release the patch [ 243 ]. Patches are potentially attractive delivery systems for oral biologics as they are able to prevent proteolysis of encapsulated proteins and peptides, and promote absorption through the intestine by forming a local drug depot with controlled, unidirectional drug release [ 238 ]. Patch-based devices have been discussed in previous reviews for the oral delivery of biologics such as bovine serum albumin (BSA) [ 242 ], insulin, exenatide [ 244 ], human GCSF [ 245 ], EPO [ 246 ] and calcitonin [ 247 ].…”

Electrospun Nanometer to Micrometer Scale Biomimetic Synthetic Membrane Scaffolds in Drug Delivery and Tissue Engineering: A Review

“…In the field of macromolecule and nanomedicine drug delivery, the molecular barrier is extensively researched with the view of achieving non-invasive delivery of the therapeutics [3,44] and the understanding of some of the component barriers of the mucosae has helped in developing effective drug delivery strategies against these barriers [45]. However, the barrier function of BM in drug delivery studies is a field that is not fully appreciated.…”