Drug-resistance to antibiotics can be overcome by the combined use of antimicrobial peptides and conventional antibiotics
The bacterial pathogens cause different infectious diseases. Therefore, antibiotic drugs are used to treat these infectious diseases. But the increase in antibiotic resistance made the treatment difficult (Miller-Petrie et al., 2017). The treatment of malaria, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and Mycobacterium tuberculosis is also resistant to drugs (WHO, 2014).
The Centers for Disease Control and Prevention (CDC) have identified some resistant bacteria, such as Clostridium difficile (C. difficile), carbapenem-resistant Enterobacteriaceae, and cephalosporin-resistant Neisseria gonorrhoeae in the United States. Both typhoidal and nontyphoidal Salmonella infections are showing drug resistance, and multidrug resistance.
Bacteria have increasingly shown resistance to first-line, second-line, and last-resort antibiotics, but the rates and trends of resistance depends on the location, organism, and antibiotics. The resistant bacteria can spread faster than ever. Drug-resistant infections are causing higher morbidity, mortality, death and medical cost. The higher medical expenses, rapid spread of infections and higher rate of antibiotic consumption are observed in the low- and middle-income countries. The guts of livestock, water and soil can be the host of resistant bacteria exposed to antibiotics. Human beings can be infected when they come into contact with animals and infected food, water, or waste.
The drug resistance, antibiotic resistance and multi-drug resistance are increasing and spreading rapidly in the people. Therefore, it is urgent to develop drugs and treatment for these drug-resistant infections. Zhu et al. (2022) made a thorough review how antimicrobial peptides (AMPs) and conventional antibiotics can show synergistic effect for the treatment of drug-resistant infections.
Antimicrobial peptides (AMPs) adopt several mechanisms to exert their antimicrobial activities rejecting the possibility of induction of drug resistance. They demonstrate great potential as new generation antimicrobial agents. However, these drugs, almost more than 30, are currently in the clinical trial phase. Some studies demonstrate that antimicrobial peptides and conventional antibiotics show synergistic effects. Therefore, if these drugs are used together, they can be more powerful antimicrobial agents, and can kill drug-resistant bacteria, stop drug resistance of bacteria, and significantly improve the therapeutic effects of antibiotics.
Reference
Miller-Petrie M, Pant S, Laxminarayan R. Drug-Resistant Infections. In: Holmes KK, Bertozzi S, Bloom BR, et al., editors. Major Infectious Diseases. 3rd edition. Washington (DC): The International Bank for Reconstruction and Development / The World Bank; 2017 Nov 3. Chapter 18. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525181/ doi: 10.1596/978-1-4648-0524-0_ch18
Zhu Y, Hao W, Wang X, Ouyang J, Deng X, Yu H, Wang Y. Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug-resistant infections. Med Res Rev. 2022 Jul;42(4):1377-1422. doi: 10.1002/med.21879. Epub 2022 Jan 4. PMID: 34984699.
Use of 3D printing technology in personalised drug design and delivery
Dr Md Anawar Hossain
What is three-dimensional (3D) printing?
It is a promising additive manufacturing technology, which can manufacture 3D objects for developing various drug delivery systems for pharmaceutical applications. Drug delivery is a system through which formulation is developed for drug manufacturing and drug transportation into human body to control disease. In the 3D printing techniques, the thermoplastic polymers or hydrogel materials are deposited in sequential layers one on top of another to produce 3D object.
Challenges and solution strategies
There are some hindrances for the application of 3D printing techniques in commercial-scale production. The current drug delivery system should be modified to produce 3D printed dosage forms with different drug release patterns and properties. The 3D printing techniques can play a role in the drug delivery and development of patient-specific medicines. However, most of the materials used in pharmaceutical manufacturing are not suitable for the current 3D printing techniques. Therefore, further research is needed to develop and adapt the 3D techniques to suit with a wider range of materials. Future research should focus on developing cost-effective printing technologies and compatible materials for these printers, which can produce a range of 3D objects.
3D printing technique in personalized medicine
The advancement of science and technologies in pharmaceutical field has created many new ideas for the design of drugs, manufacturing technology, and processes to produce high quality of dosage form. Drug delivery, development and manufacturing process emphasize the physicochemical and biopharmaceutical characteristics of Active Pharmaceutical ingredients (API) and regulatory requirement.
In a same country, there are different types of people in respect to their eating habits, profession, living styles, ethnic background and individual differences. In some multi-cultural countries, these differences are very higher than those in other countries. The patients in these countries have different ethnic backgrounds, eating habits, circadian cycles, and inter individual differences. Therefore, drug development experts encounter a lot of difficulties to deliver uniformity in manufacturing medicine considering all of the human or personal differences. Therefore, recently, it has been essential to develop personalized medicine.
Three-dimensional (3D) printing technologies can play a significant role in manufacturing personalized medicine and producing innovative formulations and disease modelling. Technological development has aided the scientist to make innovation in pharmaceutical industry. The 3D printing technologies, computer-aided drug design and modelling have accelerated the production of personalized pharmaceutical drug products. Recently, 3D printing has been successfully applied to develop pharmaceutical formulations. However, the research and development scientists need to conduct further work to optimize the formulation, processes and equipment to produce the desired shape and size of the medicines. The FDA first time approved a 3D printed drug named SPRITAM (Levetiracetam) in August 2015.
Types of 3D printing technologies
Several 3D printing technologies have been tested to develop the formulation for the solid oral dosage forms (SODFs) of medicines. Out of them, the following 3D printing technologies have been most frequently used in the production of SODFs:
A. Extrusion-Based 3DP
B. Vat photopolymerization
C. Inkjet 3DP
D. Powder-Based 3DP
Traditional versus 3D printing for tablet manufacturing
1. Traditional tablet manufacturing technology involves a number of unit operations, such as granulation, drying, milling, compression, and coating, where each of which has a number of critical processing parameters such as granulation time, drying time, mill speed, compression force etc.
2. Tablet manufacturing using 3D printing involves fewer unit operations and, as a result, fewer critical processing parameters.
3D printing over conventional manufacturing
Advantage
- 3D printing technology has two advantages for oral solid dosage forms, such as individualized treatment and precise control of drug release.
- 3D printing can reduce the cost of manufacturing complex medicines by reducing human intervention and the number of unit procedures.
- It does not use any organic solvents.
Disadvantage
- Main drawbacks of 3D printing are the lack of quality control procedures at hospitals or pharmacies, which can influence the products’ in vivo performance.
- Cyber-attack on or trouble in the computer used for 3D printing might affect the manufacturing procedures.
Use of inkjet printing in pharmaceutical preparation
This method is most widely used to produce oral disintegrating film formulations in pharmaceuticals.
Drawbacks of 3D printing in pharmaceutical applications
Although 3D printing has many benefits over convention techniques, this printing method is not widely used in the pharmaceutical industry due to the following drawbacks.
1. Lack of suitable polymers for pharmaceutical applications.
2. None of the polymers is quite safe and suited for human use.
3. They have stability concerns due to their photosensitivity.
4. Photoinitiator fragments in photo-polymerized structures can be cytotoxic.
5. Unexpected chemical interaction may occur between the photopolymer and the drug called as a Michael addition reaction.
Solutions to challenges of 3D printing in pharmaceuticals
3D printing technology has some technological challenges and constraints which need to be solved before it can be successfully used. There are some current limitations
- in the research of excipients,
- the development of printing software and tools,
- the optimization of the preparation’s mechanical properties, and
- the regulatory landscape.
References
Pund A., Magar M., Ahirrao Y., Chaudhari A., Amritkar A., 2022. 3D printing technology: a customized advanced drug delivery. Asian Journal of Pharmaceutical and Clinical Research, 15(8), pp. 23-33. Under Creative Commons License.