Nanocapsules: Tiny Vessels for Targeted Drug Delivery and Beyond

What are Nanocapsules?

Nanocapsules are nanoscale containers that can encapsulate and protect various substances, such as drugs, enzymes, or other active ingredients. These tiny capsules typically range in size from 10 to 1000 nanometers and consist of a core material surrounded by a protective shell or membrane. The core can be liquid, solid, or even gaseous, while the shell is usually made of polymers, lipids, or inorganic materials.
Ta  pH-responsive DNA origami nanocapsule (blue) loaded with an enzyme (yellow color, high pH)
A pH-responsive DNA origami nanocapsule (blue) loaded with an enzyme (yellow color, high pH). Read more. (Image: Veikko Linko, Boxuan Shen and Heini Ijäs/Aalto University)

Key Features of Nanocapsules

Nanocapsules exhibit several unique features that make them attractive for various applications:
  • Encapsulation and Protection: The shell of the nanocapsule protects the core material from degradation, oxidation, or other unwanted reactions. This protective barrier allows for the stable storage and delivery of sensitive substances, such as fragile proteins or easily degradable drugs.
  • Controlled Release: Nanocapsules can be designed to release their contents in a controlled manner, either continuously or in response to specific stimuli, such as pH, temperature, or light. This controlled release enables the precise delivery of active ingredients over extended periods or at targeted locations.
  • Targeted Delivery: The surface of nanocapsules can be functionalized with targeting ligands, such as antibodies or peptides, that recognize specific receptors on cells or tissues. This targeted delivery approach minimizes off-target effects and enhances the therapeutic efficacy of encapsulated drugs.
  • Enhanced Bioavailability: Nanocapsules can improve the bioavailability of poorly soluble or easily degradable substances by protecting them from the harsh environment of the body and facilitating their absorption across biological barriers, such as the intestinal wall or the blood-brain barrier.

Types of Nanocapsules

Nanocapsules can be classified into different categories based on their composition, structure, and preparation methods:

Polymeric Nanocapsules

Polymeric nanocapsules are prepared using biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), chitosan, or polyethylene glycol (PEG). These nanocapsules offer excellent biocompatibility, stability, and tunable release profiles. They are widely used in drug delivery and biomedical applications.

Lipid Nanocapsules

Lipid nanocapsules are composed of a lipid core surrounded by a surfactant shell. They are prepared using various lipids, such as triglycerides, fatty acids, or waxes. Lipid nanocapsules are particularly suitable for the encapsulation of hydrophobic compounds and have shown promise in topical and oral drug delivery.

Inorganic Nanocapsules

Inorganic nanocapsules are fabricated using inorganic materials, such as silica, gold, or magnetic nanoparticles. These nanocapsules offer unique properties, including high stability, magnetic responsiveness, and surface functionalization capabilities. They find applications in imaging, sensing, and targeted drug delivery.

Preparation Methods for Nanocapsules

Several methods have been developed for the preparation of nanocapsules, each with its own advantages and limitations:

Emulsion-based Methods

Emulsion-based methods involve the formation of an oil-in-water or water-in-oil emulsion, followed by the solidification of the dispersed phase to form the nanocapsule shell. Common techniques include emulsion polymerization, emulsion-solvent evaporation, and double emulsification. These methods are versatile and can be used to encapsulate both hydrophobic and hydrophilic substances.

Interfacial Polymerization

Interfacial polymerization involves the reaction of two monomers at the interface of two immiscible liquids, leading to the formation of a polymer shell around the dispersed phase. This method allows for the precise control over the shell thickness and composition, but may require the use of toxic monomers or solvents.

Nanoprecipitation

Nanoprecipitation, also known as solvent displacement, involves the rapid mixing of a polymer solution with a non-solvent, leading to the spontaneous formation of nanocapsules. This simple and scalable method is suitable for encapsulating hydrophobic substances, but may result in low encapsulation efficiencies for hydrophilic compounds.

DNA-based Nanocapsules

Recent advances in DNA nanotechnology have enabled the creation of customized DNA nanostructures that can function as nanocapsules. Researchers have built capsule-like carriers using DNA origami techniques, where a long single-stranded DNA molecule is folded into a predetermined shape with the help of short staple strands. These DNA nanocapsules can be designed to open and close in response to specific stimuli, such as changes in pH or the presence of target molecules. The programmable nature of DNA allows for the precise control over the size, shape, and functionality of these nanocapsules, making them promising candidates for drug delivery and biosensing applications.

Layer-by-Layer (LbL) Assembly

Layer-by-Layer (LbL) assembly is a versatile method for preparing nanocapsules with multilayered shells. This technique involves the alternating deposition of oppositely charged polymers or other materials onto a sacrificial template, such as a nanoparticle or an emulsion droplet. After the desired number of layers is reached, the template is removed, leaving behind a hollow nanocapsule. LbL assembly allows for the precise control over the shell thickness, composition, and functionality, and can be used to encapsulate a wide range of substances.

Self-Assembly

Self-assembly is a bottom-up approach for preparing nanocapsules, where individual building blocks, such as amphiphilic molecules or block copolymers, spontaneously organize into capsule-like structures in solution. This process is driven by non-covalent interactions, such as hydrophobic, electrostatic, or hydrogen bonding forces. Self-assembled nanocapsules can be designed to respond to various stimuli, such as pH, temperature, or light, and can be used to encapsulate and release a variety of substances.

Microfluidic Methods

Microfluidic methods involve the use of microscale channels and devices to generate nanocapsules in a controlled and reproducible manner. By manipulating the flow of immiscible fluids, such as oil and water, within microfluidic channels, researchers can create monodisperse emulsions or double emulsions that serve as templates for nanocapsule formation. Microfluidic methods offer several advantages, such as high encapsulation efficiencies, narrow size distributions, and the ability to generate complex multi-compartment nanocapsules.

Supercritical Fluid Methods

Supercritical fluid methods exploit the unique properties of substances above their critical point to prepare nanocapsules. The most common technique is supercritical anti-solvent (SAS) precipitation, where a polymer solution is rapidly mixed with a supercritical fluid, such as supercritical carbon dioxide, causing the polymer to precipitate and form nanocapsules around the encapsulated material. This method is particularly useful for encapsulating sensitive substances, as it avoids the use of high temperatures or organic solvents that may cause degradation.

Applications of Nanocapsules

Nanocapsules have found numerous applications in various fields, including:

Drug Delivery

Nanocapsules are widely explored as drug delivery systems for the treatment of cancer, infections, and other diseases. By encapsulating drugs within nanocapsules, researchers can improve their stability, solubility, and pharmacokinetics, while reducing side effects and enhancing therapeutic efficacy. Nanocapsules can be designed to target specific cells or tissues, release drugs in response to physiological triggers, or deliver multiple drugs simultaneously for combination therapy.

Food and Nutraceuticals

Nanocapsules are used in the food industry to encapsulate and protect sensitive ingredients, such as vitamins, antioxidants, or flavors. Nanoencapsulation can improve the stability and bioavailability of these compounds, mask undesirable tastes or odors, and enable the controlled release of flavors or nutrients. Nanocapsules can also be incorporated into functional foods or nutraceuticals to deliver health-promoting substances, such as probiotics or bioactive peptides.

Cosmetics and Personal Care

Nanocapsules are employed in cosmetic and personal care products to encapsulate and deliver active ingredients, such as anti-aging compounds, sunscreens, or moisturizers. Nanoencapsulation can enhance the penetration of these substances into the skin, improve their stability and efficacy, and provide controlled release over extended periods. Nanocapsules can also be used to create novel sensory experiences, such as the burst release of fragrances or the color-changing effects of pH-responsive nanocapsules.

Agriculture and Crop Protection

Nanocapsules are being explored as delivery systems for pesticides, herbicides, and other agrochemicals. By encapsulating these substances within nanocapsules, researchers aim to reduce their environmental impact, improve their efficacy, and enable targeted delivery to specific pests or weeds. Nanocapsules can also be designed to respond to environmental stimuli, such as moisture or light, to release their contents only when needed.

Challenges and Future Perspectives

Despite the immense potential of nanocapsules, several challenges need to be addressed for their widespread application. One of the main concerns is the potential toxicity and long-term safety of nanocapsules, especially when used for biomedical applications. The biodegradability and biocompatibility of nanocapsule materials must be carefully evaluated to ensure their safe use in the body.
Another challenge is the scalability and reproducibility of nanocapsule production methods. Many current techniques rely on complex and expensive processes, which may limit their industrial feasibility. The development of simple, robust, and cost-effective methods for nanocapsule preparation will be crucial for their commercial success.
Future research on nanocapsules will focus on the design of multifunctional and stimuli-responsive systems that can perform multiple tasks, such as targeted delivery, imaging, and therapy. The integration of nanocapsules with other nanomaterials, such as nanoparticles or nanofibers, will enable the creation of novel hybrid systems with enhanced properties and functions. Additionally, the exploration of natural and bioinspired materials for nanocapsule preparation will lead to the development of more biocompatible and sustainable delivery systems.

Further Reading