Peptide applications in biomedicine

Peptides, which are short chains of amino acids, have gained significant attention in biomedicine due to their diverse applications. Their unique properties, such as high specificity, low toxicity, and excellent biocompatibility, make them valuable tools for various biomedical purposes. Here are some examples of peptide applications in biomedicine:

1. Drug Discovery and Development: Peptides serve as promising candidates for drug discovery due to their ability to interact with specific targets in the body. Peptide-based drugs can be designed to mimic or block the activity of natural proteins, hormones, or enzymes. Examples of peptide-based drugs include insulin, glucagon-like peptide-1 (GLP-1) analogs for diabetes, and peptide-based anticancer drugs like goserelin and leuprolide.
2. Therapeutic Peptides: Peptides can be used directly as therapeutic agents. Some naturally occurring peptides have inherent therapeutic properties, such as antimicrobial peptides (e.g., colistin and polymyxin) that combat bacterial infections and peptide hormones (e.g., vasopressin and oxytocin) that regulate physiological processes. Synthetic peptides are also developed for therapeutic purposes, such as peptide-based vaccines for immunization against infectious diseases or cancer. The peptide 4N1Ks, a 10 amino acid peptide derived from TSP1 protein, demonstrated improved senolytic activity when delivered into nanoemulsions to senescent breast cancer cells, compared to the free peptide [1].
3. Diagnostic Tools: Peptides play a crucial role in diagnostic applications. Peptide-based biomarkers are used to detect and measure specific molecules or pathological conditions in the body. They can be used in various diagnostic techniques, including immunoassays, fluorescence imaging, and biosensors. Peptide-based imaging agents are also employed in molecular imaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI) to visualize specific tissues or biomarkers.
4. Targeted Drug Delivery: Peptides can be employed as targeting ligands to deliver drugs specifically to desired sites in the body. By conjugating therapeutic agents to targeting peptides, drug delivery systems can be designed to accumulate in specific tissues, organs, or cells. This approach increases the drug’s efficacy, minimizes off-target effects, and reduces systemic toxicity. One example is the paper published by Bouzo et al. 2021 in which they used biodegradable and biocompatible sphingomyelin nanosystems (SNs) decorated with the UroG peptide as a dual strategy for targeting metastatic colorectal cancer cells and simultaneously treat them in combination with the encapsulated the anticancer drug etoposide [2].

The applications of peptides in biomedicine continue to expand as researchers explore their potential in areas like immunotherapy, gene delivery, wound healing, and more. Peptide engineering and advances in peptide synthesis techniques are expected to further broaden the scope of their biomedical applications in the future.

Despite their great potential, their clinical translation is often hindered by poor bioavailability and stability, rapid clearance and short half-life, low membrane permeability, which hinders their ability to cross cellular barriers and reach their intended targets, immunogenicity, and challenges regarding patentability and intellectual property protection. Overcoming these hurdles is essential to unlock the full potential of peptide-based therapeutics and facilitate their successful clinical translation.

What nanotechnology can offer to overcome clinical translation hurdles?

Nanotechnology offers several advantages and opportunities to enhance peptide applications in biomedicine.

1. Improved Drug Delivery: Nanotechnology provides efficient strategies for delivering peptides to their target sites in the body. Nanoparticles can encapsulate or conjugate peptides, protecting them from degradation and enhancing their stability. These nanocarriers can improve peptide solubility, prolong circulation time, and facilitate controlled release, leading to enhanced drug delivery and improved therapeutic outcomes. For example, the recently published article by Diaz-Villares et al 2023 demonstrates a significantly increase in the retention time of a senolytic peptide for the treatment of osteoarthritis after intra-articular injection, when the peptide was loaded into biodegradable nanosystems, in relation to the free peptide [3].
2. Enhanced Peptide Stability: Peptides are susceptible to enzymatic degradation, limiting their therapeutic potential. Nanotechnology can address this challenge by protecting peptides from degradation. Encapsulation of peptides within nanoparticles or coating them with biocompatible materials provides a protective shield, preserving their structure and bioactivity during storage and delivery.
3. Targeted Delivery: Nanoparticles can be engineered to selectively target specific cells, tissues, or organs, enhancing the specificity of peptide delivery. Functionalization of nanoparticles with targeting ligands, such as antibodies or peptides, allows for site-specific accumulation and cellular internalization of the peptide cargo. This targeted delivery approach reduces off-target effects and improves the efficacy of peptide therapeutics.
4. Combination Therapies: Nanotechnology enables the development of combination therapies by co-delivering peptides and other therapeutic agents. Nanoparticles can carry multiple payloads, such as peptides, chemotherapy drugs, or imaging agents, within a single system. This approach allows for synergistic effects, simultaneous diagnosis and treatment, and personalized medicine approaches.
5. Imaging and Diagnostics: Nanotechnology-based platforms can be utilized for peptide-based imaging and diagnostic applications. Nanoparticles can be engineered to carry peptide probes that specifically bind to disease-associated biomarkers. By incorporating imaging agents onto nanoparticles, such as quantum dots or iron oxide nanoparticles, targeted imaging of specific tissues or disease sites can be achieved.
6. Controlled Release Systems: Nanotechnology offers controlled release systems for peptide delivery. Nanoparticles can be designed to respond to specific stimuli, such as pH, temperature, or enzymes, to trigger the release of encapsulated peptides. This approach allows for site-specific, on-demand release of peptides, optimizing therapeutic efficacy and reducing side effects.

 

Over the years, significant research efforts have been focused on developing novel delivery systems to overcome these limitations (nanoparticles, microneedles, and peptide conjugates). Nanoparticles have gained significant attention as carriers for peptide delivery due to their unique properties, including high surface area, tunable size, and surface modifications, which will lead to a reduction in the drug side effects and an increase in the drug’s efficacy. Among these, lipidic nanoemulsions, emerged as a promising strategy for enhancing peptide delivery.

 

DIVERSA innovative lipid nanoemulsiones for peptide applications

Our patented innovative drug delivery system based on lipid nanoemulsions opens new avenues of possibilities in the field. With its exceptional capabilities, this technology overcomes the challenges associated with peptide therapeutics, paving the way for enhanced efficacy and clinical translation. Our drug delivery technology offers a range of exceptional benefits for peptide applications in biomedicine:

GREAT ASSOCIATION EFFICIENCY:

The association efficiency is crucial for ensuring optimal loading and stability of peptides within the delivery system, which directly impacts their release kinetics and targeted delivery to the desired site.

DIVERSA technology can associate a wide variety of therapeutic peptides with different length, peptide charge, hydrophobicity, and isoelectric point, showing great association efficiencies between 70-99% (table 1) and maintaining the nanometric size below 300 nm (Fig. 2).

Table 1. Association of different peptides to DIVERSA Delivery technology.

 

 

 

 

 

 

 

 

Figure 2. Characterization of DIVERSA Peptide Delivery Reagent by Dynamic Light Scattering (DLS) showing the hydrodynamic diameter of DIVTECH associated to peptides of different length (from 12 to 28 amino acids).

 

 

 

ENHANCED STABILITY:

Peptides are prone to degradation by proteolytic enzymes (resulting in the loss of biological activity or rapid clearance from the body) both in the gastrointestinal tract and systemic circulation, which reduces their therapeutic efficacy.

From this point of view, DIVERSA delivery technology has shown a great stability in different relevant biological fluids, during storage up to 6 months in different buffers, and in culture media supplemented with FBS. The size, PdI, Zeta Potential, and the physical appearance of the peptide loaded formulations (with different length) were measure at time 0 and 24 hours later. No relevant changes in the colloidal properties were observed after 24 hours storage, showing highly stable formulation.

 Figure 3. ICH (International Council for Harmonization) long-term stability of the blank DIVERSA technology at room temperature (40 ºC, 75% RH) and under storage conditions (25 ºC, 60% RH) (a). Stability of the blank DIVTECH in different buffers and cell culture medium supplemented with FBS (b). Stability of DIVERSA technology associated to peptides of different length (from 12 to 28 amino acids) for 24 hours under storage conditions (4 ºC) (c).

 

IMPROVED CELL INTERNALIZATION:

The efficient internalization of peptides into target cells is crucial for achieving their desired therapeutic effects or facilitating specific cellular processes.

DIVERSA Peptide Delivery Reagent can efficiently enhance cellular uptake, promote endosomal escape, enable targeted delivery, protect peptides from degradation, and facilitate intracellular release, not only in vitro, but also in vivo (Figure 4, 5).

Figure 4. Uptake of fluorescent labeled DIVTECH loaded with a peptide by flow cytometry. Nearly 100% of cells become green after 2-hours incubation with DIVTECH (a). Internalization of a peptide (labelled in green) loaded DIVERSA Peptide Delivery Reagent in fibroblasts (b). Therapeutic efficiency of DIVTECH loaded with a peptide and compared to competitors and the free peptide (c).

 

It is important to note that the internalization mechanism of DIVERSA Peptide Delivery Reagents may depend on various factors, including the composition, size, surface properties, and specific interactions with the target cells. The design and formulation of lipidic nanoemulsions can be tailored to optimize their internalization efficiency and enhance the cellular uptake of peptides for therapeutic applications.

Figure 5. SUV images of one representative subject of [⁸⁹Zr]-peptide loaded DIVERSA Delivery Reagent showed as Maximum Intensity Projection (MIP). Images show the whole-body distribution of [⁸⁹Zr]-PEPTIPE-DIVTECH at different time points after intra-articular administration.

 

INTELECTUAL PROPERTY PROTECTION:

DIVERSA’S technology has been already protected by a patent constituting a solid foundation for future innovation. Not only provides intellectual property protection, but also differentiation, commercial value, market exclusivity, defense against competitors, and a pathway for continuous innovation.

Incorporating a patented drug delivery technology into your peptide molecule you could add a unique and innovative aspect to the overall invention. This differentiation can strengthen the patentability of the peptide by demonstrating a novel approach or solution to the challenges associated with its delivery. The patented technology provides a competitive advantage by offering a distinct feature that sets it apart from other existing peptide delivery methods.

Moreover, our lipid nanoemulsion drug delivery system is designed for scalability and cost-effectiveness. The manufacturing process can be efficiently scaled up to meet large-scale production demands, ensuring consistent quality and availability of the delivery system for widespread use.

 

Do you have a potential therapeutic peptide but you lack an effective delivery strategy? 

Try our PEPTIDE DELIVERY REAGENTS:  

The best way to have a first contact with our technology is without a doubt trying our ready-to-use Delivery Reagents, specifically designed for this purpose and with a user friendly methodology. However, this does not mean that we can’t help you with any questions that you may have regarding your peptide.  Please, don’t hesitate to contact us to order your DIVERSA Delivery Reagent or if you need further guidance.

Establish a CO-DEVELOPMENT AGREEMENT:  

We understand that you may wish to have a more personalized approach, and for this reason, we have created the Co-Development Agreements. In this case, we would build up a specific project for your specific project.

You can contact us or write an email to info@diversatechnologies.com. We are looking forward to helping you with your molecules!

 

References

(1) Jatal, Raneem et al. “Sphingomyelin nanosystems decorated with TSP-1 derived peptide targeting senescent cells.” International journal of pharmaceutics vol. 617 (2022): 121618. doi:10.1016/j.ijpharm.2022.121618

(2) Bouzo, B.L., Lores, S., Jatal, R. et al. Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer. Sci Rep 11, 17213 (2021). doi:10.1038/s41598-021-96578-z

(3) Sandra Díez-Villares, et al. “Quantitative PET tracking of intra-articularly administered 89Zr-peptide-decorated nanoemulsions”. Journal of Controlled Release. Vol 356 (2023). Pages 702-713. doi:10.1016/j.jconrel.2023.03.025

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