Nanomedicines for the Delivery of Biologics

Abstract

A special symposium of the Academy of Pharmaceutical Sciences Nanomedicines Focus Group reviewed the current status of the use of nanomedicines for the delivery of biologics drugs. This meeting was particularly timely with the recent approval of the first siRNA-containing product Onpattro™ (patisiran), which is formulated as a lipid nanoparticle for intravenous infusion, and the increasing interest in the use of nanomedicines for the oral delivery of biologics. The challenges in delivering such molecules were discussed with specific emphasis on the delivery both across and into cells. The latest developments in Molecular Envelope Technology® (Nanomerics Ltd, London, UK), liposomal drug delivery (both from an academic and industrial perspective), opportunities offered by the endocytic pathway, delivery using genetically engineered viral vectors (PsiOxus Technologies Ltd, Abingdon, UK), Transint™ technology (Applied Molecular Transport Inc., South San Francisco, CA, USA), which has the potential to deliver a wide range of macromolecules, and AstraZeneca’s initiatives in mRNA delivery were covered with a focus on their uses in difficult to treat diseases, including cancers. Preclinical data were presented for each of the technologies and where sufficiently advanced, plans for clinical studies as well as early clinical data. The meeting covered the work in progress in this exciting area and highlighted some key technologies to look out for in the future.

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

“…An effective cellular uptake has an impact on the therapeutic response, as many drugs are directed towards intracellular targets. Notably, an enhanced internalization is crucial for improving the activity of both biologics and small molecules, as it allows poor cellular permeability to be overcome, and the multidrug efflux transporters to be bypassed, respectively [52,53]. The most common approach to increase the NCs uptake is "active" (i.e., molecular) targeting.…”

“…Moreover, the evidence that NCs could be entrapped inside endosomes and/or lysosomes led the scientists to study this mechanism developing NCs able to reach the cell cytosol by clever strategies, including direct fusion with the plasma membrane [59] or by performing enhanced endosomal escape [82][83][84]. The use of engineered NCs can bring other opportunities, such as the encapsulation of poorly soluble drugs [85][86][87], as well as the delivery of biologics improving their bioavailability, permeability, and stability in the biological environment [53,72]. Thanks to NCs, it is possible to use drugs already accepted by clinical trials, opening the chance to administer them by different routes (i.e., topic [88], oral [89], and inhalation [90] rather than intravenous).…”

On Complex Coacervate Core Micelles: Structure-Function Perspectives

“…For these reasons, biologics are gradually becoming the new standard in the medical field. This trend is clearly manifested in the drug market sales worldwide, since many of the most profitable therapeutics available today are biologics such as enzymes, antibodies, peptides, viruses, and nucleic acids [ 33 , 34 , 35 ]. Addressing the many challenges associated with the delivery and release of biologics, including those that are in clinical use, is thus of considerable fundamental and applied interest.…”

Manufacturing of hybrid drug delivery systems by utilizing the fused filament fabrication (FFF) technology

“…The recent FDA-and industry-driven trends are moving toward addressing the current clinical needs via the existing additive manufacturing techniques [33]. On the other hand, there is a constantly growing number of new biologics approved by the FDA, accounting for sixty-nine new biologics approvals in the past few years (2014-2019) and 21% of the total approvals of therapeutics in 2019 [34][35][36], which are expected to dominate the global pharmaceutical market [37]. Similarly, several life-saving antiviral treatments are based on multi-drug administration, including treatment of, e.g., HIV and hepatitis C. Accordingly, efforts in this era to combat the pandemic COVID-19 are currently (end of March 2020) centered around multi-drug solutions [38].…”