Sanjivani Puyad*
Traditional drug delivery methods often result in poor therapeutic efficiency due to the lack of controlled release and inability to target specific tissues. Drugs administered via oral, intravenous, or topical routes frequently exhibit low solubility, rapid metabolism, and nonspecific distribution, leading to undesirable side effects and poor patient compliance [1]. Nanotechnology offers an innovative solution by developing carriers at the nanoscale capable of transporting and releasing drugs in a controlled and targeted manner [2]. Nanocarrier-based drug delivery systems (NDDS) are designed to encapsulate active pharmaceutical ingredients (APIs) within nanosized materials ranging from 1–1000 nm. Their nanoscale dimensions allow for increased surface area, improved solubility of hydrophobic compounds, and enhanced permeability through physiological barriers such as the intestinal mucosa and blood–brain barrier [3]. The concept of using nanocarriers for drug delivery was first explored with the development of liposomes in the 1960s, followed by polymeric nanoparticles, dendrimers, and lipid-based systems [4]. Over time, advancements in material science, polymer chemistry, and nanofabrication have refined these systems for greater biocompatibility and targeted drug release. Moreover, surface modification with hydrophilic polymers such as polyethylene glycol (PEG) or targeting ligands such as folate, antibodies, or peptides further enhances selectivity and circulation time [5]. Nanocarriers play a crucial role in increasing drug residence time, reducing degradation, and achieving sustained release. For instance, liposomal formulations of doxorubicin and paclitaxel have demonstrated prolonged plasma half-life and reduced systemic toxicity in cancer therapy [6]. The integration of stimuli-responsive mechanisms—where release is triggered by pH, temperature, or enzymes—further personalizes treatment to disease-specific microenvironments [7]. Table 1 summarizes the key benefits of nanocarrier-based systems compared to conventional drug delivery approaches
Table 1: Comparison between Conventional and Nanocarrier-Based Drug Delivery Systems
|
Parameter |
Conventional Systems |
Nanocarrier-Based Systems |
|
Drug solubility |
Often poor; limited for hydrophobic drugs |
Improved solubility via encapsulation |
|
Bioavailability |
Variable, often low |
Significantly enhanced |
|
Drug protection |
Limited protection from degradation |
Protects drug from enzymatic and environmental degradation |
|
Targeting capability |
Non-specific |
Site-specific via passive or active targeting |
|
Release profile |
Rapid, uncontrolled |
Sustained and controlled |
|
Side effects |
High due to systemic exposure |
Reduced due to localized delivery |
|
Patient compliance |
Moderate |
Improved due to reduced dosing frequency |
NDDS are being extensively explored in oncology, neurology, cardiology, and infectious diseases for delivering small molecules, peptides, proteins, and nucleic acids [8]. Recent innovations such as multifunctional hybrid nanocarriers and nanotheranostic systems—combining therapy and diagnostics—illustrate the versatile potential of nanomedicine [9]. Therefore, understanding the classification, design principles, mechanisms of drug release, and evaluation parameters of nanocarriers is essential for their rational development and successful clinical translation.
Classification of Nanocarrier Systems
Nanocarriers can be classified based on their composition, structural organization, and method of drug incorporation. Each system possesses distinct characteristics influencing its pharmacokinetic behavior, stability, and therapeutic performance [10]. The major types of nanocarrier systems are discussed below and summarized in Table 2.
1. Liposomes
Liposomes are spherical vesicles composed of one or more phospholipid bilayers enclosing an aqueous core [11]. They can encapsulate both hydrophilic drugs (in the aqueous phase) and lipophilic drugs (within the bilayer). Their size generally ranges from 50 to 1000 nm, and surface modification with PEG or ligands enhances circulation time and targeting ability [12]. Liposomal formulations like Doxil® and Ambisome® are FDA-approved for cancer and fungal infections. Advantages include biocompatibility, biodegradability, and versatility in drug encapsulation, whereas limitations involve stability issues and high production costs [13].
2. Polymeric Nanoparticles
Polymeric nanoparticles are solid colloidal particles prepared from biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA), chitosan, and polycaprolactone (PCL) [14]. These particles can encapsulate or adsorb drugs, providing controlled release and protection from degradation. The surface of polymeric nanoparticles can be modified with targeting ligands or hydrophilic polymers to enhance site specificity and circulation time [15]. Their biocompatibility and controlled release kinetics make them particularly useful for anticancer and peptide drug delivery.
3. Dendrimers
Dendrimers are highly branched, tree-like polymers with nanometric dimensions and well-defined architecture. Their internal cavities allow encapsulation of drugs, while terminal functional groups permit surface modification for targeted delivery [16]. Generations (G1–G10) define their size and branching complexity. Poly(amidoamine) (PAMAM) dendrimers are among the most widely studied types due to their water solubility and low toxicity [17]. They have shown promising applications in gene delivery, antimicrobial therapy, and imaging.
4. Solid Lipid Nanoparticles (SLNs)
SLNs are composed of physiologically compatible solid lipids that remain solid at room and body temperature [18]. They provide controlled drug release, excellent biocompatibility, and protection of labile drugs from degradation. Compared to polymeric nanoparticles, SLNs offer higher physical stability and scalability [19]. However, limitations include drug expulsion during storage and low loading efficiency for hydrophilic drugs.
5. Nanostructured Lipid Carriers (NLCs)
To overcome SLN limitations, nanostructured lipid carriers (NLCs) were developed by blending solid and liquid lipids. This combination improves drug loading and prevents crystallization, enhancing stability and release control [20]. NLCs are used in transdermal and oral delivery of poorly soluble drugs.
6. Polymeric Micelles
Polymeric micelles are formed by the self-assembly of amphiphilic block copolymers in aqueous media, creating a hydrophobic core and hydrophilic shell [21]. They are ideal for solubilizing poorly water-soluble drugs like paclitaxel and curcumin. Additionally, micelles can be engineered for stimuli-responsive behavior, releasing drugs under specific pH or temperature conditions [22].
7. Metallic and Magnetic Nanoparticles
Metal-based nanocarriers, such as gold, silver, and iron oxide nanoparticles, are utilized for both therapeutic and diagnostic purposes [23]. Magnetic nanoparticles can be directed to target sites using external magnetic fields and also serve as contrast agents in imaging [24]. Surface modification enhances their stability and biocompatibility.
8. Niosomes
Niosomes are nonionic surfactant-based vesicles similar to liposomes but more stable and cost-effective [25]. They encapsulate both hydrophilic and hydrophobic drugs and are widely used in topical, transdermal, and ocular delivery systems [26].
Table 2: Summary of Major Nanocarrier Systems and Their Characteristics
|
Type |
Composition |
Drug Type |
Advantages |
Limitations |
|
Liposomes |
Phospholipids, cholesterol |
Hydrophilic/ lipophilic |
Biocompatible, clinically approved |
Expensive, stability issues |
|
Polymeric nanoparticles |
PLGA, PCL, chitosan |
Small molecules, peptides |
Controlled release, versatile |
Solvent residues possible |
|
Dendrimers |
PAMAM, PPI |
DNA, proteins, small molecules |
Multivalency, precision |
Synthesis complexity, toxicity |
|
SLNs |
Solid lipids |
Lipophilic |
Stable, biodegradable |
Limited hydrophilic loading |
|
NLCs |
Solid + liquid lipids |
Hydrophobic |
Higher loading, stable |
Moderate scalability |
|
Polymeric micelles |
Amphiphilic copolymers |
Hydrophobic |
Solubilization, stimuli-responsive |
Low drug loading |
|
Metallic nanoparticles |
Gold, silver, Fe?O? |
Anticancer, imaging |
Magnetic targeting, imaging |
Cytotoxicity concerns |
|
Niosomes |
Nonionic surfactants |
Broad range |
Stable, economical |
Limited clinical data |
10.5281/zenodo.17586836