Toward Effective Long-Term Prevention of Thromboembolism: Novel Oral Anticoagulant Delivery Systems

Abstract

Despite intensive research in the field of oral anticoagulants over the last decade, simple and effective long-term prevention of thromboembolism is still an unmet need. In addition to drug discovery approaches, the development of novel oral drug delivery systems (DDSs) of clinically well-established anticoagulants presents an intriguing mean of improvement of anticoagulant therapy. The latter topic is therefore the focus of the present review. All relevant clinical trials with anticoagulants formulated in the oral DDS are reviewed, and selected preclinical examples of promising novel anticoagulant DDSs are also described. For greater understanding, a background on DDS and drug absorption from the gastrointestinal tract is also provided. Three leading approaches for the oral anticoagulant DDS are currently being investigated in clinical settings, all relying on coadministration of anticoagulants with specific carriers. In contrast to the clinical setting, a diverse range of possibilities for oral delivery of anticoagulant are being investigated in preclinical trials (e.g., nanotechnology), and it would be therefore interesting to examine their performance in clinical trials.

Biomimetic Solid Lipid Nanoparticles for Oral Bioavailability Enhancement of Low Molecular Weight Heparin and Its Lipid Conjugates: In Vitro and in Vivo Evaluation

“…Low molecular weight heparin (LMWH) is the agent of choice for treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), coronary syndromes etc . The use of LMWH clinically is limited due to parenteral administration, which necessitates trained personnel for administration, creates pain phobia and is associated with risk of needle borne infections. , Several attempts have been made to investigate nonparenteral routes (oral, nasal, pulmonary and rectal) of administration for efficient LMWH delivery so as to explore its clinical therapeutics. − Among all, the oral route is the most preferred and acceptable route of drug delivery from the patient compliance and self-administration point of view . Hence, it demands investigations in the area of oral LMWH delivery.…”

Recent Advances in the Structural Design of Photosensitive Agent Formulations Using “Soft” Colloidal Nanocarriers

“…The second absorption mechanism, passive diffusion, is based on the transport of an encapsulated cargo by the paracellular pathway. The transition of the drug occurs via the junctions between enterocytes, whereas endocytosis is a process which is characteristic for macromolecules uptake [162]. Numerous examples of nanocarriers for the oral administration of photosensitive agents are presented in Table 3.…”

In situ crosslinkable heparin‐containing poly(ethylene glycol) hydrogels for sustained anticoagulant release

“…16,17 The first systems to show limited clinical success combined heparin into oral syrups 18,19 and later into solid gel capsules 20,21 by combination with N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC), whereby SNAC acts as a carrier molecule via weak association of heparin, increasing the gastrointestinal absorption followed by dissociation once absorbed. 22 In addition, a wide range of other oral delivery strategies have been proposed (although not yet employed clinically) including covalent modification, emulsification, nanoparticle formulation, polyion complexes, and others.…”