Passive delivery of protein drugs through transdermal route

Abstract

Skin is the largest external organ in the human body but its use for therapeutic purposes has been minimal. Stratum corneum residing on the uppermost layer of the skin provides a tough barrier to transport the drugs across the skin. Very small group of drugs sharing Lipinski properties, i.e. drugs having molecular weight not larger than 500 Da, having high lipophilicity and optimum polarity are fortunate enough to be used on skin therapeutics. But, at a time where modern therapeutics is slowly shifting from use of small molecular drugs towards the use of macromolecular therapeutic agents such as peptides, proteins and nucleotides in origin, skin therapeutics need to be evolved accordingly to cater the delivery of these agents. Physical technologies like iontophoresis, laser ablation, micro-needles and ultrasound, etc. have been introduced to enhance skin permeability. But their success is limited due to their complex working mechanisms and involvement of certain irreversible skin damage in some or other way. This review therefore explores the delivery strategies for transport of mainly peptide and protein drugs that do not involve any injuries (non-invasive) to the skin termed as passive delivery techniques. Chemical enhancers, nanocarriers, certain biological peptides and miscellaneous approaches like prodrugs are also thoroughly reviewed for their applications in protein delivery.

Optimization of Sodium Deoxycholate-Based Transfersomes for Percutaneous Delivery of Peptides and Proteins

“…Several strategies have been developed to overcome the skin barrier and facilitate the permeation of peptides and proteins through the skin. This includes encapsulation of peptides and proteins in lipid vesicular system, such as transfersomes [5,6]. Transfersomes is an ultradeformable vesicle (UDV) which shows a great ability to penetrate the skin by squeeze through the pores in the stratum corneum that are less than one-tenth the diameter of the transfersomes themselves and delivering the drug to the epidermis and dermis [7].…”

Recent Advances in the Transdermal Delivery of Protein Therapeutics with a Combinatorial System of Chemical Adjuvants and Physical Penetration Enhancements

“…Nanocarriers have been innovatively designed and developed to deliver the protein therapeutics into a deep layer of the skin. These have been reported as being superior to chemical enhancers in terms of skin permeability and therapeutic stability 4a,46. Nanocarrier systems for protein therapeutics include studies using lipid‐based nanovesicles, microemulsions, and nanoparticles in this section.…”

“…Liposomes are the conventional vesicular nanocarriers exhibiting improved delivered efficacy, as compared to other topical enhancements, like creams, gels, and ointments 46a. In 1980, Mezei and Gulasekharam investigated the applicability of liposomes as a drug carrier and reported the liposomal drug delivery system enhanced drug penetration efficacy .…”

“…Depending on the lipophilicity (hydrophilic or hydrophobic) of the encapsulated drugs, the phase of the microemulsion could be designed by adjusting each component as a formulation of water‐in‐oil (W/O), or oil‐in‐water (O/W) . In particular, W/O microemulsions are suitable for entrapping the protein therapeutics, and have advantages for delivery through the skin, because the lipophilic surrounding is similar to the environment in the upper layer of skin 46a,72…”

Potential of dry powder inhalers for tuberculosis therapy: facts, fidelity and future

“…These physicochemical degradations can lead to loss of therapeutic activity. Another concern with these biomolecules is their large molecular weight, hydrophilicity of proteins and pulmonary biological fate [89][90][91]. To surpass these all issues, various researchers tried and tested different strategies for pulmonary delivery of proteins and peptides.…”