Exploring the Hidden Potential of Hollow Capsules in Controlled Drug Delivery Systems

Controlled drug delivery systems have always remained a reliable method for achieving a targeted therapeutic efficiency and minimal side-effects. Yet numerous active molecules cannot be delivered because of the diverse nature of the tissues and cells in the human body. There is still a need to develop an ideal controlled drug delivery system with multiple features like high drug loading capacity, biocompatibility, low toxicity, enhanced stability, reduced side effects, and targetoriented delivery. Advancement in polymer science and nanotechnology has given rise to a variety of targeted drug delivery techniques using different polymers and among these hollow capsules hold a prominent place.  

Synthesis of hollow capsules 

Hollow capsules are easy to fabricate; biocompatible; can load drug molecules of any nature and aid in monitoring the pharmacokinetic drug release. Common methods for the preparation of hollow capsules can be categorised as:  

  1. Self-assembly method 
  2. Template-assisted method   

 

1. Self-assembly methods There are 3 different types of self-assembly methods:  

Solvent displacement selfassembly method – It involves the preparation of a homogenous mixture of a block polymer and an organic solvent which upon addition of water forms hollow capsules by changing the orientation of hydrophilic and hydrophobic segments. The hydrophobic segments orient themselves together to minimise interaction with the aqueous environment and hydrophilic segments diffuse into the water. This orientation results in the formation of bilayer selfsealed vesicles.  

Film-hydration self-assembly method – It includes the addition of water to a preformed thin film of amphiphilic block polymers. By the addition of water, the layer of film swells and detaches from the surface slowing vesicles formation.  

2. Template-assisted methodLayer-by-layer templateassisted method is a multiple-layer deposition of polymer on a colloidal base followed by the dissolution of colloid. This method helps in controlling the thickness of the capsule cell wall during the layer deposition process.  An alternate approach called a singlestep polymer approach has been designed which includes the use of crosslinking agents to stabilise the outer single polymer membrane. This technique was introduced to skip multiple steps of layer deposition by using single constituents such as polypeptides and polyelectrolytes.  

Drug loading in hollow capsules  

The drugs can either be pre-loaded into the hollow capsules or post loaded. Preloading drugs indicate drug loading before sealing of vesicles.  Preloading can be done by either using mesoporous silica or using non-porous templates. Mesoporous silica mediated pre-loading involves the use of mesoporous silica nanoparticles as a template for drug loading due to their larger surface area and adjustable size. Postloading strategies include the use of pH or ion gradient, emulsion-mediated, and polymerdrug conjugation. pH or ion mediated loading involves the use of the difference in pH between internal and external layers of vesicles to load drugs. The emulsion mediated method involves using an oil phase to dissolve the therapeutic agent and then loading it. Polymer drug conjunction method involves anchoring of drug on the polymer which is then used to make a polymer film. Post loading however suffers from the drawback of low loading capacity and excessive time consumption as compared to pre-loading techniques. 

Drug release from hollow capsules 

The most critical aspect of designing hollow capsules is the ability to trigger drug release at the target site. The release can be achieved by using stimulusresponsive polymeric materials. 

  • Thermo-triggered release capsules are a non-invasive technique that releases the drug by external heat stimulation because inflammatory tissues have a temperature higher than other body parts.  
  • pH-triggered drug release from hollow capsules is based on the principle of protonation and deprotonation of functional groups such as carboxyls and amines present in the polymer leading to disassembly of carrier capsules and drugs on change of pH.  
  • Ultrasound-triggered drug release is another non-invasive and yet deep penetrating technique to trigger drug release. The primary principle of using ultrasound is based on its thermal effect that transmits acoustic energy to the target or oscillation effect which collapses the cavitating bubbles in the capsule wall.  
  • Light triggered release uses lightresponsive materials such as azobenzene and spiropyran in the capsule wall that undergoes cleavage of chemical bonds to release the drug.    

Takeaway  

Over the past decade, a lot of contribution has been made to develop hollow capsules because of its ability to load various therapeutic agents and easy fabrication. A greener approach to the fabrication of hollow capsules involves reducing the use of harsh chemicals during core removal in templateassisted preparation and the use of lesser steps to make capsules. A shift to the concept of green capsule synthesis approach and developing hollow capsules that can carry both hydrophilic and hydrophobic drugs and release drugs by a combination of stimuli can enhance the efficacy of hollow capsules as an efficient drug delivery system.  

References: 
  1. Quang Tran, H., Bhave, M., & Yu, A. (2020). Current Advances of Hollow Capsules as Controlled Drug Delivery Systems. ChemistrySelect, 5(19), 5537-5551. 
  2. Anselmo, A. C., & Mitragotri, S. (2014). An overview of clinical and commercial impact of drug delivery systems. Journal of Controlled Release, 190, 15-28. 
  3. Itoh, Y., Matsusaki, M., Kida, T., & Akashi, M. (2006). Enzyme-responsive release of encapsulated proteins from biodegradable hollow capsules. Biomacromolecules, 7(10), 2715-2718. 
  4. Glinel, K., Sukhorukov, G. B., Möhwald, H., Khrenov, V., & Tauer, K. (2003). Thermosensitive hollow capsules based on thermoresponsive polyelectrolytes. Macromolecular chemistry and physics, 204(14), 1784-1790. 
  5. Zhang, Y., Yang, S., Guan, Y., Cao, W., & Xu, J. (2003). Fabrication of stable hollow capsules by covalent layer-by-layer self-assembly. Macromolecules, 36(11), 4238-4240. 
  6. Caruso, F. (2000). Hollow capsule processing through colloidal templating and self‐assembly. Chemistry–a European journal, 6(3), 413-419. 
  7. Shi, J., Du, C., Shi, J., Wang, Y., & Cao, S. (2013). Hollow multilayer microcapsules for ph‐/thermally responsive drug delivery using aliphatic poly (urethane‐amine) as smart component. Macromolecular Bioscience, 13(4), 494-502. 
  8. Shen, H. J., Shi, H., Ma, K., Xie, M., Tang, L. L., Shen, S., … & Jin, Y. (2013). Polyelectrolyte capsules packaging BSA gels for pH-controlled drug loading and release and their antitumor activity. Acta biomaterialia, 9(4), 6123-6133. 
  9. Shchukin, D. G., Gorin, D. A., & Möhwald, H. (2006). Ultrasonically induced opening of polyelectrolyte microcontainers. Langmuir, 22(17), 7400-7404. 
  10. Ochs, M., Carregal‐Romero, S., Rejman, J., Braeckmans, K., De Smedt, S. C., & Parak, W. J. (2013). Light‐Addressable Capsules as Caged Compound Matrix for Controlled Triggering of Cytosolic Reactions. Angewandte Chemie International Edition, 52(2), 695-699. 

1 thought on “Exploring the Hidden Potential of Hollow Capsules in Controlled Drug Delivery Systems

  1. Effect of drug solubility on the in vitro availability rate from suppositories with lipophilic excipients The factors involved in mechanisms of availability of different drugs from suppositories with lipophilic excipients were studied by using an in vitro model of the rectal compartment with a porous membrane simulating the rectal barrier. The solubility in water of drugs was found to be the fundamental factor influencing the release rate from suppositories. In fact, following the melting of the suppository at body temperature the drug particles can migrate to the interface with the small volume of rectal secretion where they dissolve. Drug molecules can so diffuse until they come into contact with the rectal barrier through which the drug is absorbed. Drug concentration in the intrarectal aqueous phase produces the gradient against the large volume of the plasma phase. This gradient regulates the diffusion rate through the barrier. A drug with a low water solubility saturates the intrarectal phase at low concentration hindering the subsequent dissolution of the drug particles remaining in the melted excipient. This fact maintains the viscosity of the melted suppository at a ligh level, which slows the migration of the particles. On the other hand, a drug with high water solubility quickly leaves the excipient, producing a high concentration in the intrarectal phase which supports a high diffusion rate across the barrier. The results obtained indicate that drugs with low solubility in water result in low availability, while drugs with good solubility can give an intense and rapid drug supply for a rapid and intense therapeutic response with the dose administered almost completely utilised.

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