Can Peptides Be Taken Orally or Absorbed Through the Skin?
Peptides are short chains of amino acids recognized for their therapeutic and cosmetic applications. Their biological activities make them ideal candidates for pharmaceuticals and skincare formulations. However, peptides face significant challenges regarding effective delivery into the body, particularly concerning oral ingestion and skin absorption. This article explores the feasibility, challenges, and advancements in both oral and transdermal peptide delivery systems, helping readers understand the current state of peptide bioavailability and absorption technologies.
Challenges in Oral Peptide Delivery
Oral administration is generally the preferred method for drug delivery due to factors such as convenience, patient compliance, and reduced healthcare costs. However, peptides pose unique challenges when administered orally, primarily due to their susceptibility to degradation in the gastrointestinal (GI) tract.
Stability and Bioavailability Issues
The acidic environment of the stomach (gastric pH 1.5–3.5) and digestive enzymes like pepsin and pancreatic proteases significantly degrade peptides, reducing their therapeutic efficacy. For instance, the antioxidant peptide ATSHH rapidly loses its biological activity at pH 2, illustrating the instability of peptides in acidic gastric conditions (Frontiers in Nutrition).
Moreover, peptides exhibit inherently low oral bioavailability. Studies indicate that the oral bioavailability of peptides such as BPC-157 is markedly lower compared to injection-based administration due to extensive digestive breakdown (PubMed).
Innovations to Improve Oral Peptide Absorption
To address these issues, novel technologies and formulations have been developed to enhance peptide stability and absorption. Enteris BioPharma’s Peptelligence® technology exemplifies these advancements, significantly improving oral peptide bioavailability by up to 11-fold compared to traditional formulations (Enteris BioPharma). This technology employs enteric-coated tablets that protect peptides from gastric degradation, releasing the active peptide in the intestinal tract, where absorption is maximized.
Transdermal Peptide Delivery: Opportunities and Advancements
The skin, particularly the outermost stratum corneum, serves as a formidable barrier against external substances, limiting the absorption of peptides applied topically. Nevertheless, recent innovations have made significant strides in overcoming these barriers, making transdermal delivery an increasingly viable option.
Penetration Enhancers
The development of penetration enhancers has significantly improved peptide transdermal delivery. One notable example is the SPACE peptide, which has demonstrated the ability to enhance skin penetration of large molecules such as Cyclosporine A by up to five-fold without compromising skin integrity (PNAS). Such peptide-based enhancers facilitate the delivery of therapeutic molecules that were traditionally restricted by the skin’s barrier properties.
Use of Microneedle Technologies
Microneedle technologies have emerged as an innovative solution to transdermal delivery challenges. Studies published in PLOS ONE demonstrate that microneedle application can enhance the transdermal delivery of tripeptides by approximately 300% compared to passive diffusion methods. This technology creates microscopic channels in the skin, temporarily disrupting the barrier and allowing peptides to penetrate deeper skin layers effectively.
Clinical Validation through Advanced Imaging
Clinical validation has further substantiated the effectiveness of transdermal delivery methods. Collaborative research between the University of Nottingham and No7 Skincare validated the penetration of the Matrixyl 3000+™ peptide into the skin’s deeper layers using advanced 3D OrbiSIMS imaging techniques. This study provided conclusive evidence of the effective transdermal absorption of peptides used in commercial skincare products.
Comparative Overview of Oral and Transdermal Delivery Methods
The table below summarizes key aspects of oral versus transdermal peptide delivery:
| Delivery Method | Bioavailability Challenges | Technological Advancements | Clinical Validation Examples |
|---|---|---|---|
| Oral | Gastric acidity, digestive enzymes, low absorption | Enteric-coated tablets (Peptelligence®) | Peptelligence® improved bioavailability up to 11-fold |
| Transdermal | Stratum corneum barrier, molecule size restriction | SPACE peptides, microneedle technologies | Matrixyl 3000+™ peptide confirmed via 3D OrbiSIMS |
Leading Research Organizations and Contacts
Several esteemed institutions and organizations are at the forefront of peptide delivery research:
- Enteris BioPharma, innovators behind Peptelligence® technology, based in Boonton, NJ, USA.
- University of Nottingham, involved in advanced transdermal imaging studies, located in Nottingham, UK.
- Ningxia University, School of Food Science and Engineering, China, led by Prof. Songmin Cao.
- Nanjing Agricultural University, Key Laboratory of Meat Processing and Quality Control, China, led by Prof. Xinglian Xu.
- Peptide-Based Drug Research Group, University of Copenhagen, Denmark, led by Prof. Paul Robert Hansen, specializing in antimicrobial peptides.
Regulatory and Developmental Considerations
Beyond technological advancements, regulatory considerations significantly impact the development and commercialization of peptide-based products. Regulatory bodies such as the U.S. Food and Drug Administration (FDA) have established stringent guidelines for peptide drug approval, necessitating comprehensive evaluations of safety, efficacy, stability, and delivery mechanisms.
Future Directions in Peptide Delivery
The future of peptide delivery appears promising, driven by continuous technological innovations and growing clinical validations. The integration of advanced delivery platforms, such as nanoparticle carriers and enhanced penetration techniques, is expected to further overcome existing barriers, significantly broadening the therapeutic and cosmetic applications of peptides.
Advances in artificial intelligence and computational modeling further complement these developments, allowing researchers to optimize peptide formulations and predict their pharmacokinetic profiles with greater accuracy. Such tools enhance research efficiency, potentially accelerating the development of new peptide therapies and skincare products.
Peptides, despite their delivery challenges, continue to hold immense potential. With ongoing research and technological advancements, the barriers to effective oral and transdermal peptide delivery are progressively diminishing, opening new avenues for innovative therapeutic and cosmetic solutions.