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Challenges and future prospects for the delivery of biologics: oral mucosal, pulmonary, and transdermal routes

Morales, J. O ; Sharif University of Technology | 2017

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  1. Type of Document: Article
  2. DOI: 10.1208/s12248-017-0054-z
  3. Publisher: Springer New York LLC , 2017
  4. Abstract:
  5. Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers. While all these routes avoid transit through the gastrointestinal tract, each has its own strengths and weaknesses that may be optimal for specific classes of compounds. Buccal and sublingual delivery enable rapid drug uptake through a relatively permeable barrier but are limited by small epithelial surface area, stratified epithelia, and the practical complexities of maintaining a drug delivery system in the mouth. Pulmonary delivery accesses the highly permeable and large surface area of the alveolar epithelium but must overcome the complexities of safe and effective delivery to the alveoli deep in the lung. Transdermal delivery offers convenient access to the body for extended-release delivery via the skin surface but requires the use of novel devices and formulations to overcome the skin’s formidable stratum corneum barrier. New technologies and strategies advanced to overcome these challenges are reviewed, and critical views in future developments of each route are given. © 2017, American Association of Pharmaceutical Scientists
  6. Keywords:
  7. Biologics ; Buccal ; Inhalation ; Microenvironment ; Mucosal ; Pulmonary ; Skin ; Sublingual ; Transdermal ; Alpha 1 antitrypsin ; Alpha interferon ; Biological product ; Buprenorphine plus naloxone ; Calcitonin ; Captopril ; Cytochrome P450 3A4 ; Diphtheria toxin ; Dornase alfa ; Exendin 4 ; Fentanyl citrate ; Glutathione ; Gold nanoparticle ; Granulocyte macrophage colony stimulating factor ; Hepatitis B surface antigen ; Human insulin ; Insulin ; Lysozyme ; Myoglobin ; Neurotoxin ; Nisin ; Octreotide ; Pig insulin ; Progesterone ; Recombinant human insulin ; Recombinant interleukin 21 ; Salcatonin ; Salmonellosis vaccine ; Toluene ; Unindexed drug ; Active transport ; Article ; Bacterial metabolism ; Buccal drug administration ; Clinical trial (topic) ; Complex formation ; Controlled drug release ; Cystic fibrosis ; Diabetes mellitus ; Drug absorption ; Drug approval ; Drug bioavailability ; Drug delivery system ; Drug efficacy ; Drug formulation ; Drug resistance ; Drug safety ; Drug uptake ; Dry deposition ; Dry powder inhaler ; Enzyme metabolism ; Fibrosis ; First pass effect ; Food and drug administration ; Gastrointestinal tract ; Human ; Inhalational drug administration ; Insulin dependent diabetes mellitus ; Intestine transit time ; Iontophoresis ; Lung alveolus epithelium ; Malignant neoplasm ; Metered dose inhaler ; Microneedle ; Nebulizer ; Non insulin dependent diabetes mellitus ; Particle size ; Permeability barrier ; pH ; Phase 1 clinical trial (topic) ; Phase 2 clinical trial (topic) ; Phase 3 clinical trial (topic) ; Product development ; Protein degradation ; Protein structure ; Randomized controlled trial (topic) ; Skin permeability ; Sublingual immunotherapy ; Tablet ; Thermal ablation delivery device ; Transdermal drug administration
  8. Source: AAPS Journal ; Volume 19, Issue 3 , 2017 , Pages 652-668 ; 15507416 (ISSN)
  9. URL: https://link.springer.com/article/10.1208%2Fs12248-017-0054-z