Moving smaller in drug discovery and delivery

9 - BioMEMs for drug delivery applications

Micro- and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become commercially-feasible due to converging technologies and regulatory accommodation. The FDA Office of Combination Products coordinates review of innovative medical therapies that join elements from multiple established categories: drugs, devices, and biologics. Combination products constructed using MEMS or NEMS technology offer revolutionary opportunities to address unmet medical needs related to dosing. These products have the potential to completely control drug release, meeting requirements for on-demand pulsatile or adjustable continuous administration for extended periods. MEMS or NEMS technologies, materials science, data management, and biological science have all significantly developed in recent years, providing a multidisciplinary foundation for developing integrated therapeutic systems. If small-scale biosensor and drug reservoir units are combined and implanted, a wireless integrated system can regulate drug release, receive sensor feedback, and transmit updates. For example, an "artificial pancreas" implementation of an integrated therapeutic system would improve diabetes management. The tools of microfabrication technology, information science, and systems biology are being combined to design increasingly sophisticated drug delivery systems that promise to significantly improve medical care.

The Second Annual Ophthalmic Drug Development and Delivery Summit was held on 19 – 20 September 2006 in San Diego, CA, US. The 2-day symposium, having a highly focused theme, was packed with cutting-edge science, insightful overviews and networking opportunities. With a total of 11 recognized specialists presenting reviews and recent results in the advancement of ocular drug development and delivery, the invited expert speaking faculty presented the latest preclinical and clinical developments in novel ophthalmic therapies and drug delivery technology. The talks included various case studies from primary investigators and pharmaceutical companies touching upon key topics: updates on current clinical trials, study design issues, sustained delivery to the eye, views of the vitreous space as a drug reservoir, new developments in dry and wet age-related macular degeneration and diabetic retinopathy, formulation for optimal drug delivery, differences and similarities in developing drugs for the eye compared with other targets, pharmacokinetics, novel ocular delivery methods and devices, delivery of proteins and peptides, focal drug delivery, non-invasive drug delivery to the eye, neuroprotection challenges, in vitro and in vivo models for glaucoma and angiogenesis for early efficacy estimation, and toxicology. Overall, the 2-day annual symposium continues to grow as an efficient platform for fostering discussion on a range of scientific topics and challenges and avenues for building collaborative partnerships in ophthalmic drug development.

The application of micro- and nanotechnology to the biomedical arena has tremendous potential in terms of developing new diagnostic and therapeutic modalities. Recent advances in micromachining and microelectriomechanical systems (MEMS) technology have provided the opportunity to fabricate miniature biomedical devices for a variety of applications. While the majority of research has focused on the development of miniaturized diagnostic tools, researchers have more recently concentrated on the development of microdevices for therapeutic applications. The progression of microfabrication technology has enabled the creation of entirely new classes of drug delivery devices which can possess a combination of structural, mechanical, chemical, and electronic features to surmount the challenges associated with conventional systems. Some therapeutic applications of microtechnology include microneedles for transdermal delivery [1, 2], as well as various implantable systems, such as immunoisolating biocapules [3, 4] and microchips for controlled release [5, 6]. However in this research, the strengths of microfabrication and micromachining were capitalized to create a completely novel microdevice from silicon dioxide, porous silicon, and poly(methyl methacrylate) for cytoadhesive oral drug delivery with inherent features providing controlled release.

Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed.

Nanotechnology currently plays a crucial role in medicine, biology, and electronics, especially in the development of sophisticated drug delivery systems. Nanospheres and nanocarriers facilitate encapsulation, targeted delivery, and controlled release of drugs, enhancing effectiveness while minimizing side effects. Simultaneously, Artificial Intelligence (AI) has become a groundbreaking asset in pharmaceutical sciences, speeding up drug discovery, dosage formulation design, and clinical trials. AI allows for precise predictions of drug–target interactions, pharmacokinetics, and toxicity, thus streamlining lead selection and lowering development. The integration of AI and nanotechnology enhances nanomedicine by improving the design and evaluation of nanomaterials. AI-based models help forecast the toxicity of nanomaterials, their uptake by cells, and their effectiveness as therapies, accelerating the creation of new solutions for drug delivery, diagnostics, and regenerative medicine. A significant advancement is the creation of smart, responsive drug delivery systems where nanocarriers respond to biological signals and release therapeutic agents in a targeted manner, leading to better patient outcomes.

As a typical microscopic imaging technology, the emergence of the microscope has accelerated the pace of human exploration of the micro world. With the development of science and technology, microscopes have developed from the optical microscopes at the time of their invention to electron microscopes and even atomic force microscopes. The resolution has steadily improved, allowing humans to expand the field of research from the initial animal and plant tissues to microorganisms such as bacteria, and even down to the nanolevel. The microscope is now widely used in life science, material science, geological research, and other fields. It can be said that the development of microscopes also promotes the development of micro- and nanotechnology. It is foreseeable that microscopes will play a significant part in the exploration of the microworld for a long time to come. The development of microscope technology is the focus of this study, which summarized the properties of numerous microscopes and discussed their applications in micro and nanotechnology. At the same time, the application of microscopic imaging technology in micro- and nanofields was investigated based on the properties of various microscopes.

Chapter SIX - Bioinspired and biomimetic materials for oral drug delivery

In 2019, in this journal, I discussed approaches for controlling the movement of molecules, in particular macromolecules, with an emphasis on how this enabled advances in the field of drug delivery - a field that has impacted billions of people worldwide. Since 2019, there have been advances in our work and this field including a striking demonstration in which drug delivery nanoparticles were crucial to the success of mRNA therapies and the Covid-19 vaccine. In this paper, I provide updates in such areas as i) developing new methods for oral drug delivery systems, ii) delivery of molecules to specific sites of the body, iii) new types of delivery systems, and iv) examples of machine learning/artificial intelligence in these areas. I also discuss advances in mRNA technology as it relates to drug delivery and the development of nanoparticles to protect and deliver vaccines, which saved and improved the lives of hundreds of millions of people throughout the world.

Raman spectroscopy represents an upcoming analytical technique in the field of skin research and dermal drug delivery. In the last few decades, significant progress in optical equipment like lasers and detectors as well as in microscopy and software development paved the way for chemically selective three-dimensional Raman imaging with high spatial resolution. Potential applications range from analysis of physiological and pathophysiological skin conditions (e.g. non-destructive cancer detection in clinics) up to surgery guidance. In the field of drug delivery and cosmetics , Raman microscopy is successfully applied for investigating interactions with skin as well as for elucidation of drug penetration kinetics within the different skin tissue layers, thus strongly supporting rational development and improving product safety of novel skin therapeutics. This chapter provides a brief introduction about skin anatomy and dermal drug delivery systems, as well as state-of-the-art analytics in skin research. Furthermore, the potential of Raman spectroscopy for application in skin research, particularly its advantages and limitations in the field, is comprehensively elaborated. Subsequently, an overview about skin research studies applying Raman spectroscopy is given comprising various in vitro as well as in vivo implementations. Finally, employment of Raman spectroscopy for advanced diagnosis and surgery guidance are discussed and a future perspective in the field of skin research is given.

Porous-based biomaterials for tissue engineering and drug delivery applications

In this paper, a comprehensive review of recent patents concerning the molecular self-assembly of peptides, peptide amphiphiles and peptidomimetics into molecules through nanoarchitectures to hydrogels is provided. Their potential applications in the field of drug delivery and tissue engineering have been highlighted. The design rules of this rapidly growing field are centered mainly on the construction of peptides in the form of peptide amphiphiles, aromatic short peptide derivatives, all-amino acid peptide amphiphiles, lipidated peptides with single and multiple alkyl chains and peptide-based block copolymers and polymer peptide conjugates. The interest in patenting of self-assembling peptides is also driven by their type (I, II, III and IV) and their ability to form well-regulated highly-ordered structures such as β-sheets/β-hairpins, α-helices/coiled coils and to hierarchically self-organize into supra-molecular structures. The applicability of these systems in cell culture scaffolds for tissue engineering, drug and gene delivery and as templates for nanofabrication and biomineralization has inspired various groups over the globe. This resulted in development of self-assembling peptides as synthetic replacements of biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostic technologies. Furthermore, biologically derived and commercially available systems are also discussed herein along with a brief account of various awarded and pending patents in the past 10 years. An overview of the diversity of the patent applications is also provided for self-assembling systems based on nano- and/or micro-scale such as fibers, fibrils, gels, hydrogels, vesicles, particles, micelles, bilayers and scaffolds.

The Application of Microfluidics in Preparing Nano Drug Delivery Systems

This review focuses on recent trends in the binding study of various antimalarial agents with serum albumins in detail. Serum albumin has a significant role in the transport of drugs and endogenous ligands. The nature and magnitude of serum albumin and drug interactions have a tremendous impact on the pharmacological behavior and toxicity of that drug. Binding of drug to serum albumin not only controls its free and active concentration, but also provides a reservoir for a long duration of action. This ultimately affects drug absorption, distribution, metabolism, and excretion. Such interaction determines the actual drug efficacy as the drug action can be correlated with the amount of unbound drug. With the advancement in spectroscopic techniques and simulation studies, binding studies play an increasingly important role in biophysical and biomedical science, especially in the field of drug delivery and development. This review assesses the insight we have gained so far to improve drug delivery and discovery of antimalarials on the basis of a plethora of drug-serum protein interaction studies done so far.

Abstract: Due to micro-/nanorobots having several propulsion mechanisms, drug delivery through micro/nanorobots is moving to the forefront of nanomedical research. However, low biocompatibility and low imaging efficiency have become major obstacles in the further development of micro- /nanorobots. This article firstly introduces the application of micro-/nanorobots in the field of nanomedicine in recent years, expresses the importance of micro-/nanorobots in terms of nanomedicine, and then summarizes and compares several propulsion mechanisms. The improvement and optimization of the preparation methodologies and structures in terms of micro-/nanorobots are also reviewed. The imaging effect and biocompatibility of micro-/nanorobots have been improved to the extent that it is suitable for clinical medicine while ensuring the efficiency of drug delivery. Then, the advantages of different propulsion mechanisms, imaging effects, and biocompatibility are compared. The aim of the review is to enable people of various knowledge backgrounds to learn directly and choose suitable modified methods based on realistic situations. Finally, future development trends and further prospects of micro-/nanorobots are discussed.