Campbell Brooks, the Commissioning Editor of Therapeutic Delivery, looks back at recent issues of the journal and shares their top three papers, which include research into injectable delivery systems to treat jawbone infections and computational algorithms to accerlerate early drug product life cycles.
Firstly, our October issue features an excellent Review article from Pujol-Navarro et al. and colleagues from the Universities of Strathclyde and Glasgow (UK). As always with new therapeutics, many drug delivery systems that appear promising in preclinical studies fail to show satisfactory efficacy in clinical trials; in this Review, the authors discuss the preclinical and clinical development of antibody- and aptamer-based therapies for multiple myeloma.
Though the survival rates for multiple myeloma have increased in recent years, due in part to the successful application of proteosome inhibitors, immunomodulatory agents and anti-CD38 antibodies, relapse is inevitable for most patients. Novel antibodies, antibody-drug conjugates, aptamers, and aptamer-drug conjugates are currently under study in clinical trials that have reached Phase III for antibodies such as Elotuzumab, and may deliver more durable therapies than those currently available. However, treatment resistance remains a significant factor limiting the success of these therapies; it is currently unclear whether aptamer-based therapies will suffer the same treatment resistance as antibody therapies because aptamer therapies are generally at earlier stages of development and the data does not yet exist.
The authors also discuss the computational modeling of peptide-drug interactions in order to screen drug candidates for efficacy against certain receptors. Molecular docking simulations may also be useful in investigating therapy durability and treatment resistance by modeling the complex interactions that occur during aptamer/antibody/protein interactions, and evidence from these simulations may facilitate design of treatments that anticipate and forestall common resistance pathways.
We await the results of the ongoing clinical trials, and hope that these promising therapies will provide a greater range of therapeutic options to patients with multiple myeloma, allowing for the application of more personalized treatment approaches.
Jawbone infections may arise from the migration of bacteria from tooth decay or dental caries into other tissues in the head and neck. Usual treatment of jawbone infections involves incision and drainage of the infected site, sometimes accompanied by root canal treatment and always accompanied by the oral or systemic administration of antibiotics such as Metronidazole. However, drugs delivered via these routes have low bioavailability in the jawbone due to the low number of blood vessels supplying the affected sites.
In this Research Article, Shreshtha Dash, Somnath Singh, and Alekha Dash of Creighton University (OH, USA) report the development of an injectable Metronidazole delivery system that forms a gel when delivered to the affected site, thereby allowing the localized and sustained release of the antibiotic. The optimized formulation utilizes poly(DL-lactide-co-glycolide) nanoparticles, for early release, and microparticles, for slower release, to encapsulate Metronidazole – all of which are combined in a poly(DL-lactide) gel. The formulation demonstrated sustained drug release over 1 week, favorable rheological properties such as syringeability, and low toxicity to human cells, thereby serving as a ‘proof-of-concept’ that may be further developed to be used for in vivo studies.
Accelerating pre-formulation investigations in early drug product life cycles using predictive methodologies and computational algorithms
Finally, in our November issue, we feature a Special Report from Harsh Shah and colleagues from J-Star Research (NJ, USA) on the uses of predictive and computational methodologies to support and inform pre-formulation studies.
Taking a more industrial perspective, the authors reflect on the fundamentals of pre-formulation studies (such as solubility, permeability, drug-excipient compatibility, etc.), and discuss computational tools that can be useful in understanding and guiding drug development at the pre-formulation stage.
Particularly interesting in this article is the discussion of solid form screening, which reviews computational tools for the crystal structure prediction of drugs and polymorphs (including co-crystals, hydrates and solvates, and salts) to ensure that all possible drug forms are accounted for as early as possible in the development pipeline, pre-empting possible complications during the manufacture of the target drug form, or even problems with the clinical activity of drugs due to unwanted drug forms occurring in the formulation.
Looking to the future, the authors highlight the computational modeling of drug-protein and drug-DNA interactions as being a current challenge due to the size and complexity of these systems. They also note the accessibility of computational tools, which do not always have ‘user-friendly’ interfaces, may be an issue since the programs themselves are niche and suggest that greater uptake of these tools will lead to more commercially available and accessible technologies.
That concludes my top picks of issues 10, 11 and 12 of Therapeutic Delivery ! I look forward to reviewing the top content of issues 13, 14 and 15 in a few months’ time.
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Our latest issue can be found here: www.future-science.com/toc/tde/current
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