Bioavailability refers to the relative extent and rate at which an active pharmaceutical ingredient (API) is released from its dosage form and absorbed into the systemic circulation in its active form. It is a fundamental pharmacokinetic parameter that determines how effectively a drug can exert its therapeutic action. A compound must first reach systemic circulation before interacting with its target site; therefore, bioavailability directly influences onset of action, therapeutic intensity, and duration of effect.
Oral administration remains the most common and economical route of drug delivery due to its simplicity and convenience. However, the actual bioavailability of many orally administered drugs is often below 30% because of factors such as first-pass metabolism, enzymatic degradation, poor aqueous solubility, and low permeability across the intestinal epithelium. This inefficiency forces higher dosing, increasing the risk of systemic side effects, waste of active materials, and environmental burden. A formulation with higher bioavailability enables lower dosing frequency, greater therapeutic consistency, and improved patient compliance, while also reducing production and material costs.
Drug absorption and systemic distribution are governed by a complex interplay of physicochemical properties, physiological conditions, and formulation characteristics. On the molecular level, parameters such as solubility, particle size, crystal lattice energy, partition coefficient (LogP), and ionization constant (pKa) determine a compound's ability to cross biological membranes. Drugs with large molecular size, high crystallinity, or suboptimal LogP values typically exhibit limited membrane permeability.
From a physiological perspective, factors such as gastric emptying rate, intestinal pH gradient, mucus layer thickness, efflux transporters (e.g., P-glycoprotein), and hepatic first-pass metabolism act as sequential barriers that limit drug absorption and systemic exposure.
At the formulation level, conventional solid dosage forms such as tablets or capsules often disintegrate into aggregated particles with low effective surface area, restricting dissolution within the short gastrointestinal transit time. This leads to sharp peak–trough fluctuations in plasma concentration profiles, which may compromise both therapeutic consistency and tolerability.
Traditional formulation strategies for improving bioavailability, such as salt formation, crystal form modification, addition of surfactants, or dose escalation, are often constrained by physicochemical and process limitations.
Dose escalation increases systemic exposure and gastrointestinal irritation risks.
Salt formation or polymorphic conversion can improve solubility but may compromise stability or process control.
Surfactant-assisted solubilization enhances dissolution transiently but may disrupt intestinal barrier integrity with prolonged exposure.
Micronization can reduce particle size to the 5–10 μm range, but increased surface energy often causes reaggregation, rapidly diminishing dissolution advantages.
These approaches have reached their practical limits within the micrometer scale. A paradigm shift toward nanotechnology-based systems offers a new pathway to overcome solubility, permeability, and metabolic barriers simultaneously.
Nanoparticle technology reduces drug particle size to the nanometer scale, typically below 200 nm, dramatically increasing surface area and interfacial energy. According to the Kelvin and Noyes-Whitney equations, both saturation solubility and dissolution rate rise as particle size decreases. For instance, curcumin nanocrystals exhibit a 12-fold increase in apparent solubility and a 9-fold enhancement in maximum plasma concentration (Cmax) compared with the raw material, while absolute bioavailability improves from 1% to 35%. Similar results have been reported for paclitaxel, fenofibrate, and itraconazole, typical Biopharmaceutics Classification System (BCS) class II compounds, achieved through purely physical size reduction or high-pressure homogenization without altering molecular structure or chemical activity.
Nanoparticles can enhance epithelial permeability through multiple mechanisms. Surface modification with positively charged polymers or targeting ligands enables multivalent interactions with intestinal microvilli, opening tight junctions or triggering endocytic uptake. For example, chitosan-coated poly(lactic acid) nanoparticles carrying insulin demonstrated a 6.4-fold increase in relative bioavailability compared to insulin solution. Solid lipid nanoparticles, owing to their structural similarity to biological membranes, can be absorbed via M-cell-mediated transcytosis into the lymphatic circulation, thereby bypassing hepatic first-pass metabolism. For long-chain fatty-acid-based formulations, lymphatic transport efficiency has been reported to rise from approximately 2% to 45%, substantially reducing hepatic exposure and improving systemic efficiency.
Nanocarrier systems can physically shield encapsulated drugs from harsh gastrointestinal environments. Polymer or lipid shells act as protective barriers against acidic hydrolysis and enzymatic degradation. For example, lactoferrin-modified nanoparticles released less than 8% of their payload in simulated gastric fluid (pH 1.2) over 4 hours, preserving the integrity of acid-labile peptides. Upon entering the ileum, the shell undergoes bile-salt-mediated hydrolysis, enabling rapid release and efficient absorption, resulting in a 28-fold improvement in the oral bioavailability of salmon calcitonin. In addition, certain nanocarriers can inhibit efflux transporters such as P-glycoprotein through competitive interactions, further increasing the net absorption fraction.
Nanoparticle-based systems allow precise control over drug release kinetics through coupled diffusion, erosion, and degradation mechanisms. By adjusting polymer composition, lipid chain length, or surface coating thickness, tailored release profiles can be achieved to match therapeutic requirements. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with silymarin, for instance, demonstrate zero-order release with an extended half-life of approximately 18 hours, maintaining stable plasma concentrations with once-daily administration. Similarly, orally administered solid lipid nanoparticles can form a "deep lymphatic reservoir," releasing the encapsulated drug gradually into the bloodstream. This mechanism tripled the systemic exposure (AUC) of ibuprofen while reducing gastrointestinal adverse effects by nearly 40%. Sustained and controlled release not only ensures prolonged pharmacological activity but also minimizes plasma concentration fluctuations, enhancing therapeutic predictability and reducing dose-related side effects.
Fig.1 Nanocarriers for drug delivery overview1,2.
BOC Sciences provides versatile nanoparticles with diverse compositions and functional modifications, customized solutions for your delivery needs.
Particle size and surface properties are critical determinants of a nanocarrier's pharmacokinetic behavior and tissue distribution. Nanocarriers within the 10-200 nm range generally achieve an optimal balance between systemic circulation time and tissue penetration. Particles below 100 nm can effectively traverse the intestinal mucus layer, while those around 50-80 nm show enhanced lymphatic transport efficiency. Particles smaller than 30 nm may undergo rapid renal clearance due to their high surface area, necessitating precise size control to maintain adequate systemic exposure.
Surface charge and interfacial chemistry further influence circulation dynamics and interactions with biological components. Weakly cationic surfaces (+5 to +10 mV) enhance adhesion to negatively charged mucosal or epithelial surfaces, improving retention and absorption. Excessive positive charge, however, may induce hemolysis or inflammatory responses. Surface modification with zwitterionic or dense polyethylene glycol (PEG) brushes neutralizes zeta potential, generates a hydration layer, and imparts "stealth" properties. This reduces non-specific protein binding and phagocytic uptake, thereby extending circulation half-life and increasing the probability of target site accumulation.
Ligand-mediated functionalization enables nanocarriers to actively recognize and bind specific cell types or tissues, significantly enhancing delivery precision. Optimal ligand density, typically 1-2 mol%, ensures effective receptor engagement without inducing saturation or off-target interactions. Various targeting moieties, including small molecules, peptides, and polysaccharides, can direct nanocarriers to tissues with high receptor expression or to specific intracellular compartments. In oral delivery, ligands such as bile acid derivatives or vitamin analogs can exploit endogenous transporters in the intestinal epithelium, promoting site-specific absorption in the distal small intestine. Parenterally administered nanoparticles benefit similarly from surface ligands that promote preferential uptake in tissues expressing the complementary receptor, enhancing local drug concentration while reducing systemic exposure and non-target interactions.
Biocompatibility and biodegradability are fundamental for the safe application of nanocarriers. Ideal materials should degrade into non-toxic metabolites following payload delivery, eliminating accumulation and associated risks. Synthetic polymers such as polylactic acid (PLA), PLGA, and polycaprolactone (PCL) degrade predictably into carbon dioxide and water. Lipid matrices composed of triglycerides or fatty acid esters mimic endogenous lipoproteins and are enzymatically cleaved into physiologically acceptable components. Natural polysaccharides such as chitosan, alginate, and hyaluronic acid provide additional advantages, combining mucoadhesion with transient modulation of epithelial tight junctions, thereby enhancing intestinal permeability for macromolecular drugs. Green manufacturing approaches, including ethanol-water azeotropic systems or supercritical CO2 processes, minimize organic solvent residues and support environmentally sustainable production.
Stimuli-responsive nanocarriers constitute an advanced strategy for controlled, site-specific drug release. These systems can respond to internal signals, such as pH variations, enzymatic activity, redox potential, or mechanical forces, as well as external stimuli, including light, temperature, or magnetic fields. For example, pH-sensitive copolymers remain hydrophobic under acidic conditions but ionize and swell in near-neutral intestinal environments, enabling selective drug release at the target site. Redox-sensitive nanoparticles crosslinked with disulfide bonds can rapidly dissociate within the intracellular high-glutathione environment, achieving higher intracellular drug concentrations compared with conventional formulations. Integration with external stimuli allows remote, non-invasive control over drug release, providing spatiotemporal precision and enhanced delivery efficiency.
Lipid-based nanocarriers, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), are widely used to enhance solubility and absorption of poorly water-soluble drugs. Liposomes, composed of phospholipid bilayers, can encapsulate both hydrophilic and hydrophobic compounds and exhibit high biocompatibility due to their structural similarity to biological membranes. SLNs utilize solid lipids with drug molecules embedded in lattice imperfections, offering superior physical stability and low leakage rates. NLCs introduce small amounts of liquid lipids into the solid lipid matrix, disrupting crystallinity to increase drug loading capacity and reduce premature drug release. Lipid-based carriers administered orally can enter the lymphatic system via chylomicron-mediated transport, bypassing hepatic first-pass metabolism and improving systemic drug exposure.
Polymeric nanoparticles offer precise control over structure, degradation, and release kinetics. PLGA nanoparticles can be tailored by adjusting the lactide-to-glycolide ratio to achieve degradation profiles ranging from one week to several months. PEGylation provides steric hindrance and hydrophilicity, prolonging circulation and minimizing protein adsorption. Chitosan nanoparticles, with intrinsic positive charge, form polyelectrolyte complexes with negatively charged mucus, extending residence time and transiently opening epithelial tight junctions, which significantly improves the oral absorption of macromolecules. Polymeric systems collectively provide a versatile platform for programmable, sustained, or targeted drug release.
Inorganic nanoparticles exploit unique physicochemical properties for high-capacity drug loading and controlled release. Mesoporous silica nanoparticles feature tunable pore sizes and high surface area, supporting drug encapsulation and stimulus-responsive surface modifications. Gold nanoparticles, inert and easily functionalized, can enhance cellular uptake via membrane interactions and enable photothermal-triggered release. Superparamagnetic iron oxide nanoparticles (SPIONs) can be guided using external magnetic fields, concentrating drugs in specific regions and enabling remotely triggered release, demonstrating high potential for site-specific, non-invasive delivery.
Nanoemulsions and polymeric micelles are efficient strategies for improving oral bioavailability of poorly water-soluble drugs. Nanoemulsions are thermodynamically stable dispersions of immiscible liquids stabilized by surfactants, with droplet sizes ranging from 20–200 nm. They increase interfacial area and facilitate dissolution and absorption, and when medium-chain triglycerides are used as the oil phase, lymphatic transport can significantly enhance systemic exposure. Polymeric micelles, formed via self-assembly of amphiphilic block copolymers, encapsulate hydrophobic drugs within the core, while the hydrophilic shell ensures solubility and colloidal stability. These micellar systems maintain structural integrity under dilution and allow co-loading of multiple drugs, enabling synergistic solubilization and absorption enhancement, providing a versatile platform for complex oral formulations.
The most immediate advantage of nanoparticle formulations lies in their dramatically increased surface area. When particle size is reduced from the micrometer to the nanometer scale, the contact area with gastrointestinal fluids increases by orders of magnitude. According to dissolution kinetics principles, drug dissolution rate is directly proportional to surface area. Nanoparticles therefore dissolve more rapidly and reach supersaturation in the intestinal lumen, generating a strong concentration gradient that drives passive absorption. This mechanism is particularly relevant for Biopharmaceutics Classification System (BCS) Class II compounds with low solubility and high permeability, effectively overcoming dissolution-limited absorption and expanding the available absorption window. For instance, reducing particle size below 200 nm can accelerate peak concentration attainment and enhance absolute bioavailability significantly.
Nanoparticles can exploit active cellular transport mechanisms to traverse the intestinal epithelium, independent of passive diffusion. They are internalized through multiple endocytic pathways, including clathrin-mediated, caveolin-mediated, and macropinocytosis processes, as well as alternative routes such as CLIC/GEEC. Once internalized, nanoparticles can undergo transcytosis, moving from the apical to the basolateral side of epithelial cells and releasing their payload into the systemic circulation. This pathway is particularly valuable for macromolecular or hydrophilic drugs that are otherwise poorly permeable, broadening the range of therapeutics that can be efficiently delivered orally.
Lipid-based nanoparticles, in particular, can be selectively absorbed by intestinal Peyer's patches and enter the lymphatic circulation. Through the thoracic duct, they bypass the portal vein and hepatic first-pass metabolism. This route significantly enhances the systemic availability of drugs susceptible to hepatic enzymatic degradation, such as certain anticancer and antiviral agents. Surface properties, such as moderate hydrophobicity, can mimic natural chylomicron surfaces, promoting binding to lymphatic endothelial receptors and extending circulation time, further improving the fraction of intact drug reaching systemic circulation.
Surface-modified nanoparticles, for example via PEGylation, reduce plasma protein adsorption and recognition by the reticuloendothelial system, resulting in extended blood circulation times. Prolonged circulation enhances the probability of drug accumulation in target tissues. Furthermore, in regions with leaky vasculature and impaired lymphatic drainage, such as inflamed or tumorous tissues, nanoparticles preferentially extravasate and are retained, achieving passive targeting and local drug enrichment. This enhanced permeability and retention (EPR) effect prolongs the duration of drug activity at the site of interest and can reduce systemic fluctuations, thereby supporting more consistent therapeutic exposure.
In vitro models serve as a critical first step for evaluating nanoparticle performance. Dissolution studies using simulated gastrointestinal media allow direct comparison of release rates and extent between nanoparticle and conventional formulations. Permeation studies employing Caco-2 monolayers or artificial membranes can simulate intestinal absorption and quantify improvements in transcellular transport conferred by nanoparticles. These data provide predictive insight into in vivo behavior and guide formulation optimization.
Pharmacokinetic studies quantify the systemic exposure achieved by nanoparticle formulations. Blood sampling over time allows calculation of parameters such as area under the concentration–time curve (AUC), peak concentration (Cmax), time to peak concentration (Tmax), and half-life (t1/2). Comparative AUC analysis between nanoparticle and reference formulations reflects the magnitude of bioavailability enhancement. Bio-distribution analysis using fluorescent or radiolabeling techniques enables real-time tracking of nanoparticles, revealing tissue accumulation patterns, clearance pathways, and targeting efficiency.
Ensuring reproducibility and performance consistency of nanoparticles requires comprehensive physicochemical characterization. Key parameters include particle size distribution and polydispersity index (measured via dynamic light scattering), surface charge (ζ-potential), morphology and core–shell structure (via transmission electron microscopy), and pore characteristics for mesoporous carriers. Drug loading, encapsulation efficiency, and stability under storage and physiological conditions are essential metrics, as they determine release kinetics and in vivo fate. Thermal analysis, such as differential scanning calorimetry, can verify drug amorphization, correlating with dissolution enhancements.
Establishing IVIVC models enables the prediction of in vivo pharmacokinetics from in vitro dissolution or permeation data. Convolution-based approaches link release profiles to systemic exposure, providing a quantitative relationship between formulation performance and pharmacokinetic outcomes. A robust IVIVC allows rapid, cost-effective screening of formulations and reduces reliance on extensive in vivo studies, facilitating accelerated development of nanoparticle-based drug products. Validated models can define in vitro release criteria that reliably predict bioavailability, supporting routine quality control and release testing.
Many small-molecule compounds with high pharmacological activity face significant limitations due to poor aqueous solubility. Nanoparticle technology offers several strategies to overcome these challenges:
Nanocrystal Formation: Reducing drug particles to the nanometer scale dramatically increases their specific surface area, accelerating dissolution rates and extent. This rapid dissolution ensures that drugs achieve supersaturation in the gastrointestinal tract, creating a strong concentration gradient that enhances absorption efficiency.
Carrier-Based Systems: Lipid-based nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, as well as polymeric nanoparticles, can encapsulate poorly soluble small molecules. These carriers improve apparent solubility and, in the case of lipids, facilitate lymphatic transport, enabling the drug to bypass metabolic degradation pathways and improving systemic availability.
Peptides and proteins offer high specificity, potency, and safety but face multiple oral delivery challenges, including degradation by gastric acid and enzymes and restricted permeation through intestinal mucosa. Nanoparticle systems provide integrated protection strategies:
Protection Against Enzymatic Degradation: Biodegradable polymer-based nanoparticles act as protective shells, shielding peptides and proteins from enzymatic breakdown in the gastrointestinal environment.
Enhanced Transcellular Transport: Surface functionalization with cell-penetrating peptides (CPPs), such as TAT peptides, can significantly improve nanoparticle uptake across intestinal epithelial membranes, promoting effective absorption.
Intelligent Release Designs: Environment-responsive systems, such as pH-sensitive nanoparticles, allow site-specific drug release within the intestine, optimizing oral bioavailability and therapeutic efficiency.
Gene therapeutics, including siRNA and mRNA, face challenges from cellular membrane barriers and in vivo instability. Nanoparticles, particularly lipid nanoparticles (LNPs), have become the dominant non-viral delivery platforms:
Stable Encapsulation and Delivery: Cationic lipids condense and encapsulate negatively charged nucleic acids into structurally stable nanoparticles, protecting them from nuclease degradation during transport.
Enhanced Cellular Uptake and Endosomal Escape: Nanoparticles functionalized with CPPs improve endocytic uptake, efficiently delivering nucleic acids into the cytoplasm. Ionizable lipids can undergo conformational changes under endosomal acidic conditions, promoting nucleic acid release—a critical step for gene silencing or protein expression.
Many bioactive natural compounds, including polyphenols, vitamins, and omega-3 fatty acids, suffer from poor solubility and chemical instability. Hybrid nanoparticle encapsulation systems offer significant advantages:
Hybrid Encapsulation Platforms: By combining natural polymers (e.g., chitosan, starch) with synthetic materials (e.g., PLGA, mesoporous silica), nanoparticles protect sensitive bioactives and provide controlled release capabilities.
Enhanced Stability and Absorption: These systems safeguard active compounds during food processing, storage, and gastrointestinal transit while improving their absorption, ensuring that nutritional or functional benefits are fully realized.
Table 1. Recommended Nanoparticle Products for Enhanced Bioavailability.
| Product Name | Description | Inquiry |
| Liposomes | Composed of phospholipid bilayers, capable of encapsulating both hydrophilic and hydrophobic drugs, highly biocompatible, suitable for small molecules and protein/peptide delivery. | Inquiry |
| Solid Lipid Nanoparticles | Drugs embedded in lipid lattice defects, offering high physical stability and low leakage, improving oral absorption and controlled release. | Inquiry |
| Nanostructured Lipid Carriers | Incorporates small amounts of liquid lipid in the solid lipid matrix, enhancing drug loading and delaying release, optimizing systemic exposure. | Inquiry |
| PLGA Nanoparticles | Biodegradable polymer with tunable degradation, enabling controlled and programmable drug release for oral or targeted formulations. | Inquiry |
| PEGylated Nanoparticles | Surface PEGylation prolongs circulation time, reduces protein adsorption, and enhances in vivo stability. | Inquiry |
| Chitosan Nanoparticles | Positively charged, enhances mucoadhesion and transcellular transport, suitable for oral protein/peptide delivery. | Inquiry |
| Mesoporous Silica Nanoparticles (MSN) | High surface area with tunable pore size, easily functionalized for efficient drug loading and stimulus-responsive release. | Inquiry |
| Gold Nanoparticles | Chemically inert, easily functionalized, enhances cellular uptake, can be used for photothermal-triggered release or targeted delivery. | Inquiry |
| Nanoemulsions | Thermodynamically stable, increase interfacial area, improve solubility and absorption of poorly water-soluble drugs, suitable for lipid-soluble natural compounds. | Inquiry |
BOC Sciences designs and synthesizes tailored nanoparticles based on the physicochemical properties and delivery requirements of each drug.
Functionalized Nanocarriers: Multifunctional delivery platforms can be engineered to provide high drug loading, targeted delivery, controlled release, and environment-responsive release properties.
Material Innovation: Advanced biodegradable and biocompatible polymers are synthesized with precisely controlled charge density, hydrophobic components, and structural modifications, providing the foundational materials for efficient drug delivery.
Nanoparticle performance depends heavily on material composition and surface characteristics.
Diverse Material Library: BOC Sciences offers an extensive selection of synthetic phospholipids, PEG derivatives, block copolymers, magnetic nanoparticles, gold nanoparticles, and natural polymer derivatives.
Surface Engineering and Functionalization: Services include conjugation of targeting ligands (e.g., antibodies, RGD peptides), fluorescent or radiolabeling, and PEGylation to achieve long circulation, active targeting, or imaging capabilities.
Robust characterization ensures reproducibility and performance reliability of nanoparticle formulations.
Comprehensive Physicochemical Analysis: Key analyses include particle size distribution, zeta potential, morphology, drug encapsulation efficiency, and loading capacity.
In Vitro Performance Assessment: Dissolution and permeation studies predict in vivo absorption potential, providing critical data to guide formulation optimization.
Table 2. Nanoparticle Development & Characterization Services at BOC Sciences.
| Service Name | Description | Inquiry |
| Custom Nanoparticle Synthesis | Design and synthesize lipid, polymeric, or inorganic nanoparticles tailored to drug properties, improving bioavailability and stability. | Inquiry |
| Nanoparticle Surface Functionalization | PEGylation, targeting ligand conjugation, fluorescent or radiolabeling to enhance circulation time, targeting, or traceability. | Inquiry |
| Nanomaterial Screening & Optimization | Selection and modification of lipid, polymer, or inorganic nanoparticle materials to meet drug loading, stability, and controlled release requirements. | Inquiry |
| Nanoparticle Size & Morphology Analysis | Dynamic light scattering, zeta-potential, and TEM analysis to ensure uniformity and structural stability. | Inquiry |
| Drug Loading & Release Evaluation | Assess encapsulation efficiency, loading capacity, and in vitro release profiles to optimize nanoparticle drug delivery performance. | Inquiry |
| In Vitro Absorption Assessment | Evaluate nanoparticle permeability and absorption using Caco-2 or simulated gastrointestinal models, predicting oral bioavailability. | Inquiry |
| Nanoparticle Stability Testing | Assess storage and physiological condition stability to ensure consistent nanoparticle performance. | Inquiry |
BOC Sciences emphasizes close collaboration with clients to address complex formulation challenges.
End-to-End Support: From initial concept design and formulation screening to scalable process development, interdisciplinary teams and microengineering techniques ensure comprehensive project support.
Addressing Technical Bottlenecks: Solutions focus on enhancing drug loading, controlling nanoparticle size distribution, and improving reproducibility, accelerating the translation of nanotechnology-based formulations into viable products.
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