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Stream/Area:
-
Subject:
-
Paper ID:
IJSREM63114
Volume:
10 |
5 |
May 2026
Pages:
1-10
Publication Frequency:
Monthly (12 issues per year)
License:International Journal of Scientific Research in Engineering and Management follows the Creative Commons Attribution 4.0 (CC BY 4.0) License, allowing free use and distribution with proper attribution.
Department of Pharmaceutics
Dr. Uttamrao Mahajan College of B. Pharmacy, Chalisgaon
Diabetes mellitus remains a major global health burden and estimates have shown that over 537 million people across the globe are infected with the disease. Such an epidemiological scale highlights the urgency to find new treatment approaches that can enhance glycemic control levels within a population. Although the conventional methods of administering insulin by injection into the subcutaneous tissue are foundational in the management of diabetes, several limitations associated with the therapy make them prone to compromise the treatment cost. Suffering, needle phobia, and fluctuating kinetics of absorption often lead to poor glycemic activities and decreased compliance in patients. The pulmonary route turns out to be attractive as a non-invasive method, which relies on the large surface area of the alveoli (about 140 m2), the extremely thin lining of the wall and the rich vascular system, which also allows the rapid uptake of the delivered drugs into the system. These physiological and anatomical properties of the respiratory tract qualify it as an attractive route of administration of biologics like insulin. Biodegradable polymers have been considered in nano-encapsulation of insulin such as poly(lactic-co-glycolic acid) (PLGA) and chitosan to reduce enzymatic breakdown and improve pulmonary deposition. The further conversion of these nanoparticles into inhalable dry powders through the application of techniques like spray drying or freeze drying is a complex procedure that will enhance the pulmonary bioavailability without causing drug degradation.This review of the literature will explore the science behind pulmonary insulin delivery, outline the pathophysiology of diabetes mellitus, and briefly review the progress of nano-encapsulation technologies. In addition, we specify the formulation strategies of dry powder inhaler (DPI) and the critical parameters of characterization, which define the performance of a product such as fine particle fraction (FPF), mass median aerodynamic diameter (MMAD) and drug entrapment efficiency (DEE). The pharmacodynamic performance in vitro and in vivo is critically evaluated to give an insight into the translational nature of these technologies. The clinical evidence of the currently marketed inhalable insulin products, that is, Exubera and Afrezza, are considered in the context of the developing research on the nanoparticle-based DPI systems. It is followed by the discussion of the aspect of stability, the issues of regulations and the perspectives of the translation of nano-encapsulated inhalable insulin to the routine clinical practice. We synectically summarize evidence that nano-encapsulated inhalable insulin dry powders have a high potential of providing rapid and reproducible glycemic control and improving patient adherence among Type 1 and Type 2 diabetes mellitus patients.
KEYWORDS
Nano-encapsulated inhalable insulin dry powder is a scientifically sound and a clinically compelling method of overcoming the pharmacokinetic and compliance barriers of current subcutaneous insulin treatment. With optimisation of spray-drying techniques and choice of intelligent excipients, the overlap of more advanced nano-encapsulation technology based on biodegradable polymers (PLGA, chitosan), lipid-based carriers, and optimisation of MMAD in the 1-5 µm respirable range, FPF of over 40 and drug entrapment efficiencies of over 60-80, inhalable dry powders with MMAD can be produced. In vivo and preclinical in vitro experiments indicate that it exhibited rapid onset of hypoglycaemic effect (10-20 minutes Tmax), great pulmonic bioavailability (25-40%), and increased glycaemic control (24-48 hours) compared to plain inhaled insulin. Clinical effectiveness of Afrezza(r) confirms the pulmonary route as a viable method of systemic insulin delivery, and the enhanced protective properties as well as bioavailability of nanoparticle encapsulation has a potential in next-generation products which have higher performance and wider applicability to patients. The remaining challenges of bioavailability reproducibility, long-term pulmonary safety, scale-up manufacturing and regulatory characterisation will also be important in ensuring that this promising technology, which is tested in the laboratory, is translated to clinical reality that can ultimately benefit the 537 million people with diabetes across the globe.
[1] International Diabetes Federation. IDF Diabetes Atlas, 10th edition. Brussels, Belgium: International Diabetes Federation; 2021. ISBN: 978-2-930229-98-0. Available from: https://www.diabetesatlas.org [2] American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S19–S40. doi: 10.2337/dc23-S002. [3] Karmakar S, Bhowmik M, Laha B, Manna S. Recent advancements on novel approaches of insulin delivery: focus on inhalable systems and dry powder formulations. Medical Novelties in Technology and Devices. 2023;19:100253. doi: 10.1016/j.medntd.2023.100253. [4] Feng X, Chen Y, Peng Y, Wang Y, Li L, Huang Y, Zhang Y, Liu Q. Opportunities and challenges for inhalable nanomedicine in respiratory disease treatment. International Journal of Nanomedicine. 2024;19:4469–4491. doi: 10.2147/IJN.S461020. [5] Naureen F, Shah Y, Rehman MU, Chaubey P, Nair AK, Khan J, Shah KU. Inhalable dry powder nano-formulations: advancing lung disease therapy—a review. Frontiers in Nanotechnology. 2024;2:1403313. doi: 10.3389/fnano.2024.1403313. [6] Imenshahidi M, Kabiri M, Jandaghi M, Razavi Rouhani SS, Abnous K, Karimi GR. Pulmonary delivery of insulin by dry powder inhaler formulations. Iranian Journal of Basic Medical Sciences. 2025;28(1):1–15. doi: 10.22038/IJBMS.2024.79989.17299. [7] Omidian H. Dry powder inhalers for delivery of synthetic biomolecules: modern advances and systemic applications. Pharmaceutics. 2025;17(2):175. doi: 10.3390/pharmaceutics17020175. [8] Chan HW, Zhang Y, Leung SSL, Chan JGY, Kwok PCL, Chan HK. Inhalable nanoparticle-based dry powder formulations for pulmonary drug delivery: challenges and strategies for clinical translation. Journal of Controlled Release. 2023;370:160–182. doi: 10.1016/j.jconrel.2023.08.044. [9] Cao J, Xu Y, Zhang J, Fang T, Wu F, Zhen Y, Wang D. "Nano-in-micro" structured dry powder inhalers for pulmonary delivery: advances and challenges. Journal of Drug Delivery Science and Technology. 2024;85:105648. doi: 10.1016/j.jddst.2024.105648. [10] Islam N. Dry powder inhaler design and particle technology in pulmonary delivery of biologics and nanoparticles. Journal of Pharmaceutical Sciences and Technology. 2024;16(3):145–162. doi: 10.47071/jpst.2024.16.3.145.
Publication Date
5/13/2026
Peer Review Type
Double-Blind Peer Review
Review Rounds: 2
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