1Government College of Pharmacy Karad
2Shri Ganapati Institute of Pharmaceutical Sciences and Research, Tembhurni
A significant proportion of new drug candidates suffer from poor water solubility, posing challenges in their development and effective delivery, particularly via parenteral routes. Polymeric micelles, composed of amphiphilic block or graft copolymers, have emerged as promising nanocarriers to overcome this limitation. These micelles possess a core-shell structure, where the hydrophobic core encapsulates poorly soluble drugs and the hydrophilic shell ensures colloidal stability and prolonged circulation. The self-assembling nature of these carriers enables enhanced solubility, improved drug loading, reduced toxicity, and site-specific targeting, especially to tumors via the Enhanced Permeability and Retention (EPR) effect. Preparation techniques such as dialysis, solvent evaporation, freeze-drying, and oil/water emulsification offer flexibility for incorporating a wide range of drugs. Critical characterization parameters include size, shape, critical micelle concentration (CMC), stability, and drug release behavior. Additionally, functionalization of micelles enables stimuli-responsive behavior such as pH-sensitivity, enabling controlled drug release in acidic tumor environments. Several polymeric micelle formulations have advanced to clinical trials, highlighting their clinical relevance. Their nanoscale size, biocompatibility, and structural adaptability make polymeric micelles a versatile platform for delivering hydrophobic drugs, macromolecules, and genes. This review outlines their synthesis, properties, advantages, and therapeutic applications in modern drug delivery systems.
Many new potential drugs (40% or more) have poor water solubility, making it difficult to administer them parenterally and slowing down the drug development process(1). Polymer science advancements have enabled the design of colloidal systems, such as polymeric micelles, which can accumulate in solid tumors, improve drug loading and therapeutic efficacy, enhance targeting through surface modification. Polymeric micelles consist of hydophobic core, hydrophilic shell (corona), covalently attached blocks or grafts(2). The versatility of micelles produced from amphiphilic copolymers as self-assembled nanostructures (≈10 to 200 nm) has signalled significant advances in biomedical area due to their varying functions and clinical success(3). The core of polymeric micelles acts as a reservoir for hydrophobic bioactives, while the shell provides required colloidal stability. The shell plays an important role in preventing opsonization, protein adsorption and together with the small size of polymeric micelles when accumulated in tissues with leaky vasculature through enhanced permeation and retention effect (EPR). Long circulation of these carriers can be prevented by glomerular filtration(4). There are limited formulation approaches to solubilize poorly water-soluble drugs. Common methods include:
1. Salt formation or pH adjustment (limited to ionizable drugs and risks precipitation)
2. Using cosolvents (e.g., propylene glycol, ethanol) for non-ionizable drugs(1).
Polymeric micelles are generated in an aquatic environment by the self-assembly of amphiphilic block copolymers. They have a nanoscopic, usually spherical, core/shell structure, with the hydrophobic core acting as a microreservoir for the encapsulation of hydrophobic medicines, proteins, or DNA, and the hydrophilic shell interacting with the biological media. The adaptability of the core/shell structure is what distinguishes polymeric micelles from other colloidal delivery techniques. The chemical flexibility of the polymeric micellar structure enables the development of custom made carriers that can be tailored to the physicochemical properties of the incorporated drug, disease pathophysiology, site of drug action, and proposed route of administration(5). Variations in the chemical structure of the core-forming block in polymeric micelles may be used to improve drug encapsulation, enhance micellar stability and control the rate of drug release from the carrier. The chemical structure of the micelle-forming block copolymer may also be modified to change the biological destination of the polymeric micellar carrier, enhance their specificity for an organ or tissue, or make them responsive to an external stimulus, thereby enhancing the targeting efficiency of the drug carrier. To this end, polymeric micellar delivery systems have mostly been designed and used to refine three critical parameters in drug performance: solubility, release and biological distribution(6).
Structure
The structure of polymeric micelles follows and exemplifies the similar structure of micelles proposed as per different miceller theories. It is comprised of a core, which is usually a hydrophobic section while the exterior, which is also known as corona, represents a hydrophilic block of the copolymer structure (Fig. 1). In the past two decades, several different polymers have been reported to play the role as a core or corona with their own added merits which has been utilized extensively in drug delivery and targeting. The following paragraphs would comment on the different types of polymers used for hydrophilic and the hydrophobic block of a polymeric micelle(7).
Rutuja Savakhande*, Shailesh Pendor, Dr. A. H. Hosmani, Shweta Patil, Rajlaxmi Patil, Rutuja Kadam, Sampada Potdar, Saniya Momin, Rohini More, Polymeric Micelles: A Review of Their Synthesis, Characterization, Types & Applications, Int. J. Sci. R. Tech., 2025, 2 (7), 23-32. https://doi.org/10.5281/zenodo.15777815
10.5281/zenodo.15777815
