Abstract
Pickering emulsions are novel emulsions stabilized by solid particles adsorbed at the droplet interface. Compared with conventional surfactant-based emulsions, they exhibit superior anti-coalescence stability and biosafety, and have attracted growing research interest in pharmaceutics in recent years. Beyond dermal delivery, novel oral and injectable Pickering emulsion drug delivery systems have been developed recently. These systems can mitigate surfactant-induced skin irritation, enhance transdermal drug permeation, improve oral drug absorption and chemical stability, enable controlled release and targeted delivery, and act as carriers for innovative immunological adjuvants, demonstrating broad application prospects. Numerous factors govern the fabrication of Pickering emulsion delivery systems, yet systematic reviews analyzing these influential factors remain scarce. This paper summarizes pharmaceutical applications of Pickering emulsions, elaborates on their preparation and characterization as drug carriers, and highlights how solid particles, oil phases, manufacturing processes, and multi-factor interactions modulate the construction of Pickering emulsion delivery systems. Major challenges and prospective research directions in this field are further discussed, aiming to provide theoretical references for in-depth investigations of Pickering emulsion drug delivery platforms.
Key words: Pickering emulsion; drug delivery system; solid particle; nanocrystal; oral administration; transdermal delivery; injection
1 Introduction
Emulsions stabilized by solid particles instead of traditional surfactants, termed Pickering emulsions, have garnered widespread research attention. Surpassing surfactant emulsions in coalescence resistance, low toxicity and environmental compatibility [1–3], Pickering emulsions have been extensively deployed in chemical engineering, food processing and cosmetic industries [4,5]. Lately, pharmaceutical investigations, particularly their utilization as drug carriers, have proliferated rapidly [6]. Despite their promising translational potential as delivery vehicles, research on Pickering emulsion formulations remains in its nascent stage. Fabricating stable drug-loaded Pickering emulsions constitutes the fundamental prerequisite for developing Pickering emulsion delivery systems. While a multitude of parameters dictate emulsion formation, comprehensive systematic analyses of these variables are absent in existing literature. This review recapitulates advances in Pickering emulsion delivery systems from three dimensions: pharmaceutical applications, fabrication protocols and characterization methodologies. It emphasizes the regulatory roles of solid particulates, oil phases, preparation techniques and interactive effects among diverse factors, and dissects prevailing bottlenecks and future research avenues, to support the development of next-generation Pickering emulsion-based drug delivery systems.
Table 1 Representative Pickering emulsion drug delivery systems
| Model drug | Solid particle | Type of emulsion | Route of administration | Main characteristics |
| Caffeine | Hydrophobic silica HDK® H20 | W/O | Topical | The pseudo-steady state flux and cumulated amount of caffeine after 24 h exposure for Pickering emulsion were 3 and 2.1 times those of classical emulsion, respectively. After 24 h exposure, caffeine in the receptor fluid, dermis and epidermis was 12.7%, 0.8% and 0.3%, respectively[9]. |
| Retinol | Hydrophobized fumed silica HDK® HKS D | O/W | Topical | High storage of retinol inside the stratum corneum was favored by the Pickering emulsion, showing Pickering emulsion a promising drug penetration vehicle either for targeting the stratum corneum or aiming at slow release of drug from stratum corneum which could be used as a reservoir to the deeper layers of skin[10]. |
| Methyl salicylate | Starch modified by octenyl succinic anhydride | O/W | Topical | The type of oil affected the cosmetic and rheological properties of the emulsion but did not affect the transdermal diffusion in vitro. The pseudo-steady state flux of methyl salicylate across pig skin from emulsions prepared with miglyol, paraffin and sheanut oil were all about 8 g·(cm2 h)-1, which was double that of drug solution[11]. |
| Econazole nitrate | Cyclodextrin | O/W | Topical | The rheological behavior showed that Pickering emulsion remained compatible for topical applications. The Pickering emulsion loaded econazole nitrate was able to inhibit fungus and bacterial growth (C. albicans and S. aureus), thus being expected to be used for epidermal/dermal skin targeting[13]. |
| Rutin | Self aggregated chitosan particles | O/W | Topical | The release of rutin from Pickering emulsion was almost 100% within 24 h. The sustained release of rutin in a solubilized form as well as the synergistic effect of other components of the prepared Pickering emulsion increased wound healing effect compared with the control group, which made the rutin-loaded Pickering emulsion be an effective pharmaceutical formulation for the cutaneous wound healing[14]. |
| Retinol | Block copolymer nanoparticles of poly (lactide)-block-poly (ethylene glycol) | O/W | Topical | Loading drug inside both oil droplets and block copolymer nanoparticles enhanced skin absorption of drugs. More accumulation of retinol in the stratum corneum, epidermis and dermis were observed for the Pickering emulsion compared with the surfactant-based emulsion and an oil solution[15]. |
| Bupivacaine | Cyclodextrin | O/W | Topical | Bupivacaine in Pickering emulsion was released over an extended period with a releasing ratio of 12.2%–23.1% after 48 h. Pickering emulsion could regulate the target site of skin depending on various types of oil used. Ring-structured oil allowed the highest permeation amount through skin and linear chain oil showed the highest skin- retaining amount after 24 h of exposure[16]. |
| Minocycline | Aluminum starch octenylsuccinate | O/W | Topical | Although Pickering emulsion could not prompt drug to permeate through the entire skin layer, it provided a prolonged minocycline release, always above its minimum inhibitory concentration against Staphylococcus aureus, which made it effective against superficial infections caused by S. aureus through topical administration[17]. |
| Aspirin | Silica nanoparticles possessing 50% silanol groups | O/O | Topical | The special non-aqueous Pickering emulsion could be used for transdermal formulations and exhibit high drug loading capacity. In addition, the presence of silica nanoparticle layer around oil droplets could limit the in vitro release of the aspirin with a cumulative aspirin release of 46.8% after 8 h[18]. |
| Amphotericin B | Starch CAPSUL® | O/W | Oral cavity | The antifungal activity of amphotericin B in Pickering emulsion was enhanced upon incubation with α-amylase, which showed that Pickering emulsion had a potential to deliver hydrophobic antifungal compounds to treat oral candidiasis[19]. |
| Ibuprofen | Mg(OH)2 nanoparticles | O/W | Oral | Pickering emulsion could not only protect patients from the side effects of acid medicines but also could contribute to the increase of the bioavailability of these drugs, because Mg(OH)2 had an advantage of being solubilized in an acid medium leading to the destabilization of Pickering emulsion and the release of ibuprofen orally[20]. |
| β-Carotene | Pea protein isolate | O/W | Oral | Gel-like Pickering emulsion could be formed at oil fractions (ϕ) of 0.6, which exhibited a low release of β-carotene, and high stability towards degradation during the digestion[21]. |
| Caffeine | Magnesium oxide nanoparticles | W/O | Oral | Pickering emulsion afforded sustained release of caffeine within 48 h following zero order kinetics. It also showed good growth inhibition of hepatocellular carcinoma (HepG2) and elicited significant hepatoprotection. So this formula could act as an economical approach to multiple therapy and afford safe effective sustained level for caffeine[22]. |
| Curcumin | Fe3O4@ cellulose nanocrystals | O/W | Oral | Pickering emulsion could increase stability of curcumin by 40 folds compared with the solution and prolong release of curcumin, totally 53.30% over a 4-day period. It effectively inhibited the human colon cancer cells growth down to 18% in the presence of external magnetic field and resulted in 2-fold reduction on the volume of the 3-D multicellular spheroids of HCT116 as compared to the control sample, suggesting that the special Pickering emulsion could be a promising yet effective drug delivery system for magnetic-triggered release of bioactive and therapeutics[23]. |
| Silybin | Silybin nanocrystals | O/W | Oral | Pickering emulsion of silybin could be stabilized by nanocrystals of silybin itself. The AUC of Pickering emulsion was increased by 3.8-fold and 1.4-fold compared with silybin coarse powder and nanocrystal suspension, respectively[24]. |
| Puerarin | Puerarin nanocrystals | O/W | Oral | Puerarin nanocrystals could stabilize Pickering emulsion of Ligusticum chuanxiong essential oil without any other stabilizers. The relative bioavailability of Pickering emulsion to puerarin coarse powder suspension, nanocrystal suspension, and surfactant-based emulsion were 262.43%, 155.92%, and 223.65%, respectively[25]. |
| Antigen | PLGA nanoparticles | O/W | Injection | Pickering emulsion enhanced the recruitment, antigen uptake and activation of antigen-presenting cells, potently stimulating both humoral and cellular adaptive responses, and thus increasing the survival of mice upon lethal challenge, which may provide an effective and safe strategy to enhance adaptive immunity against infections and diseases[26]. |
| Oseltamivir phosphate | Molten glycerol monostearate nanoparticles | W/O | Injection | Oseltamivir phosphate encapsulated in Pickering emulsions displayed a near linear release profile over 30 days, which significantly reduced cell viability in the human PANC-1 pancreatic cancer cell line for up to 30 days[27]. |
2 Pharmaceutical Applications of Pickering Emulsions
Dermal delivery represents the earliest and most extensively investigated application of Pickering emulsions. Such formulations alleviate skin irritation triggered by surfactants in conventional emulsions, tune drug release kinetics, and facilitate epidermal penetration or full-thickness transdermal permeation [7–18]. Additional reported applications include topical oral delivery for oropharyngeal candidiasis treatment [19], oral administration to boost bioavailability of poorly water-soluble drugs [20], sustained drug release [21,22], and targeted therapy for colorectal cancer [23].
Novel oral and injectable Pickering emulsion platforms have emerged in recent studies, including drug nanocrystal self-stabilized Pickering emulsions (DNSPE) [24,25], subcutaneously injectable Pickering emulsions serving as immunoadjuvant carriers [26], and long-acting injectable water-in-oil (W/O) Pickering emulsions [27]. In DNSPE systems, partial drug molecules dissolve in aqueous or oil phases, while residual drug exists as nanocrystals adsorbed at droplet interfaces to function as stabilizers. This design minimizes latent biosafety risks posed by exogenous solid particulates, elevates drug loading capacity, and enables co-encapsulation of poorly soluble pharmaceuticals and volatile oils. It delivers an innovative oral delivery strategy for poorly soluble drugs, especially complex herbal compound preparations. Table 1 summarizes representative reported Pickering emulsion drug delivery systems, illustrating their considerable translational value.
3 Fabrication and Determinants of Pickering Emulsion Drug Delivery Systems
Standard Pickering emulsion preparation protocols blend a drug-containing internal phase with an external phase dispersed with solid particles. Mechanical homogenization disperses the internal phase into fine droplets suspended in the continuous phase, with solid particles adsorbing onto droplet surfaces to suppress coalescence and stabilize emulsions. Solid particle and oil phase physicochemical properties act as core determinants of emulsion formation and stability, alongside manufacturing techniques and synergistic interactions between all variables.
3.1 Impacts of Solid Particles
During particle-droplet collision, approximation and interfacial adsorption, particle intrinsic properties—notably wettability, particle size and inter-particle electrostatic interactions—exert dominant effects on Pickering emulsion formation [28].
3.1.1 Particle Wettability
Consensus across most studies identifies solid particle wettability as the decisive factor governing Pickering emulsion assembly [7,29]. Optimal interfacial adsorption efficiency requires particles to possess moderate amphipathic wettability: wettable by both aqueous and oil media without complete dissolution in either phase. Wettability is quantitatively characterized by the three-phase contact angle. Generally, contact angles approaching 90° favor robust emulsion formation; highly hydrophobic particles (contact angle near 180°) or strongly hydrophilic particles (contact angle close to 0°) fail to generate stable emulsions [30]. Previous research demonstrates Pickering emulsions form exclusively when particle contact angles range from 30° to 150° [31].
3.1.2 Particle Size
Studies confirm stable Pickering emulsions demand solid particles at least one order of magnitude smaller than emulsion droplets [30]. Reducing particle size facilitates emulsion generation, enhances colloidal stability, and yields smaller droplet diameters [32,33]. Elmotasem et al. [22] fabricated caffeine-loaded W/O Pickering emulsions using magnesium oxide nanoparticles (average size 94.6 nm) and micrometer-scale MgO particles (average size 541.9 nm). Emulsions stabilized by nanoparticles exhibited average droplet sizes of 665.9 nm and remained intact for two months at ambient temperature, whereas micro-particle-stabilized emulsions displayed average droplet diameters of 1763 nm, obvious creaming and coalescence after one week, and complete phase separation within one month. Smaller nanoparticles feature lower interfacial free energy, enabling superior adsorption at oil-water interfaces to construct uniform protective particle layers that inhibit droplet fusion.
Nevertheless, conflicting evidence indicates excessive particle miniaturization (below 10 nm) impairs emulsion stability [34]. Ultra-fine nanoparticles possess adsorption free energies far lower than thermal kinetic energy, triggering spontaneous particle aggregation rather than interfacial anchoring, or prompting desorption from oil-water interfaces.
Particle size is modulated by manufacturing parameters such as high-pressure homogenization duration and pressure [24], as well as aqueous phase pH, particularly for charged particulates including proteins, cellulose and chitosan, and solid particles of weakly acidic or basic drugs. When developing oral sustained-release Pickering emulsions stabilized by soy protein, Shao et al. [21,35] only obtained stable formulations at pH 3, as soy protein self-assembles into nanoparticles solely under this pH condition. Analogous phenomena were observed in our DNSPE research [36]: ferulic acid and puerarin failed to form intact DNSPE at pH 5, with full phase separation within 24 hours; adjusting aqueous pH above 11 yielded Pickering emulsions stable for over seven days. Further characterization revealed ferulic acid and puerarin form 200–300 nm nanocrystals at pH 11, whereas particle sizes expand to 4–5 μm at pH 5. Tuning aqueous pH to manipulate solid particle dimensions therefore represents an effective strategy to construct stable Pickering emulsions.
3.1.3 Particle Concentration
Our research on silybin-based DNSPE [24] verified that drug loading dosage drastically regulates emulsion assembly and droplet size. At silybin dosages of 100 mg or 200 mg, insufficient drug nanocrystals fail to fully coat oil droplets, yielding large droplet diameters due to incomplete interfacial coverage. At a 300 mg loading dose, abundant drug nanocrystals form continuous interfacial coatings, reducing average droplet size. Further increasing drug dosage induces negligible variations in droplet morphology and diameter.
Dammak et al. [37] prepared soybean oil-water Pickering emulsions stabilized by 38.4 nm chitosan nanoparticles, identifying particle concentration as the primary stability modulator. Elevating chitosan nanoparticle concentration from 0.2% to 1.1% (w/w) improves emulsion stability via three mechanisms: (1) amphipathic chitosan segments reduce oil-water interfacial tension; (2) higher particle concentrations generate thicker, denser interfacial adsorption films; (3) elevated aqueous phase viscosity decelerates droplet collision and coalescence rates. However, excessive chitosan nanoparticle loading compromises stability. Once interfacial adsorption saturation is achieved, surplus nanoparticles disperse within the continuous phase, amplifying inter-droplet attractive forces that overcome electrostatic repulsion and trigger droplet flocculation.
3.1.4 Particle Surface Charge
Most literature corroborates high particle zeta potential facilitates emulsion stabilization. Droplet surface charge correlates positively with stabilizer particle charge: elevated particle zeta potentials strengthen electrostatic repulsion between droplets to suppress coalescence [38]. Xia et al. [26] manufactured antigen-loaded subcutaneously injectable Pickering emulsions stabilized by ~100 nm PLGA nanoparticles of varying molecular weights. Emulsions formulated with 42 kDa and 72 kDa PLGA exhibited pronounced droplet size shifts after two weeks storage, while 13 kDa PLGA-stabilized emulsions maintained consistent droplet dimensions, attributed to higher carboxylic acid end-group density and superior zeta potential of low-molecular-weight PLGA.
Conversely, excessive particle surface charge hinders interfacial adsorption. Charged particles approaching oil-water interfaces encounter repulsive barriers induced by image charges; intense electrostatic repulsion may overpower convective driving forces directing particles toward interfaces, preventing stable Pickering emulsion formation [39]. For specific particulate stabilizers such as cellulose nanocrystals, low zeta potential triggers mild inter-particle flocculation, constructing three-dimensional network architectures that moderately enhance emulsion stability [40].
Particle surface charge is intrinsically determined by molecular structure, with aqueous phase pH serving as an additional critical regulator. Luo et al. [41] fabricated oral Pickering emulsions stabilized by flavonoid particulates, observing significantly elevated particle zeta potential and enhanced emulsion stability under alkaline aqueous conditions. Adding inorganic salts such as NaCl to modulate aqueous ionic strength also tunes droplet size and colloidal stability by altering electrostatic interactions [42]. Incorporating NaCl into taro starch-stabilized Pickering emulsions neutralizes negative surface charges on starch nanoparticles, reducing particle zeta potential and promoting tighter interfacial adsorption to shrink droplet diameters and boost stability. Excess NaCl diminishes inter-droplet electrostatic repulsion and accelerates coalescence; optimal stability occurs at NaCl concentrations of 0.04–0.06 mmol·L⁻¹.
3.2 Impacts of Oil Phase
3.2.1 Oil Phase Physicochemical Properties and Molecular Structure
Common oil phases utilized in Pickering emulsion delivery systems include isopropyl myristate, oleic acid, medium-chain triglycerides, olive oil, soybean oil, wheat germ oil, palm oil and rapeseed oil. Oil composition modulates particle wettability to dictate emulsion assembly. Our investigations on herbal DNSPE [43] screened multiple oil media and confirmed emulsion stability correlates closely with three-phase contact angles at oil-water interfaces. For instance, puerarin exhibits an 82.14° contact angle in ligusticum oil/water systems, while tanshinone IIA displays a 99.2° contact angle in Capmul C8/water mixtures; emulsions formulated with these respective oil phases demonstrate optimal colloidal stability.
Oil phases exert unique regulatory effects on cyclodextrin (CD)-stabilized Pickering emulsions via wettability-independent mechanisms. CD molecules form inclusion complexes with oil molecules, with polar CD backbones oriented outward and uncomplexed hydrophobic oil segments forming terminal hydrophobic tails. Self-assembled CD-oil complexes adsorb onto droplet surfaces for stabilization, rendering complex integrity the primary determinant of emulsion stability [13]. Hu et al. [16] evaluated six oil media and concluded oil molecular dimensions must match CD cavity sizes to form hydrogen-bonded inclusion complexes for stable emulsions. Among triglyceride oils, medium-chain triglycerides only form intact emulsions with α-CD, whereas castor oil generates stable formulations with both α-CD and β-CD.
3.2.2 Oil Phase Volume Fraction
Most studies report excess oil impairs emulsion stability under fixed particle concentrations. Asfour et al. [14] prepared rutin-loaded Pickering emulsions stabilized by chitosan nanoparticles, with rutin dissolved in propylene glycol/oleic acid mixtures (1:9, v/v). Increasing oil volume fractions enlarged droplet diameters and degraded colloidal stability at constant chitosan loading. Contrastingly, Li et al. [44] fabricated curcumin Pickering emulsions stabilized by whey protein nanoparticles, obtaining stable formulations across oil volume fractions of 5%–50%. Dual stabilization mechanisms operate across variable oil ratios: oil fractions below 30% produce small ~220 nm droplets for intrinsic colloidal stability; oil fractions exceeding 40% increase system viscosity to slow droplet mobility and offset larger droplet dimensions.
3.3 Impacts of Manufacturing Protocols
Reported Pickering emulsion fabrication approaches are categorized as one-step and two-step methods, with the two-step protocol dominating current research. The two-step technique first disperses solid particles within the continuous phase to generate nanoparticulate suspensions, followed by addition and emulsification of the dispersed phase. Sonication and high-pressure homogenization represent primary emulsification techniques; high-pressure homogenization produces smaller, monodisperse droplets and enjoys wider adoption. Homogenization pressure, duration and cycle number modulate final emulsion characteristics. Our silybin DNSPE research [24] demonstrated increasing homogenization pressure reduces drug nanocrystal size, with minimal dimensional variation above 100 MPa.
The initial dispersion medium for solid particles dictates emulsion type. Curcumin, a highly hydrophobic particulate stabilizer, forms W/O Pickering emulsions when pre-dispersed in oil, while aqueous pre-dispersion generates oil-in-water (O/W) emulsions [45,46].
Laredj-Bourezg et al. [15] developed one-step fabrication for Pickering emulsions stabilized by PLA-b-PEG or PCL-b-PEG block copolymers. Acetone solutions containing block copolymers, retinol and oil phases are dropwise added to water under stirring, enabling simultaneous mechanical oil dispersion and spontaneous copolymer micellization. Acetone is removed via vacuum evaporation at 40 °C to yield finished emulsions. Droplet size and polydispersity exhibit no significant disparities between one-step and two-step protocols, yet manufacturing methodology alters model drug retinol distribution: one-step emulsions retain 1%–3% retinol within aqueous phases, whereas two-step formulations contain no aqueous retinol.
3.4 Interactive Effects Between Multiple Variables
Parameters governing Pickering emulsion assembly do not operate independently but exert synergistic or antagonistic cross-regulatory effects. Leclercq et al. [13] manufactured CD-stabilized Pickering emulsions and identified narrow optimal ratio ranges for water, oil and CD to sustain colloidal integrity; threshold ratios shift drastically across different oil media (liquid paraffin, isopropyl myristate) and CD isoforms (α-, β-, γ-CD), confirming reciprocal interactions between stabilizer molecular structure, oil composition and phase volume ratios. Particle concentration and dispersed phase volume represent two core determinants of droplet size with proven interactive behavior. Sy et al. [20] demonstrated negligible particle concentration effects on droplet dimensions at oil-nanoparticle ratios below 2%, while elevating particle loading above the 2% threshold rapidly expands droplet diameters from 100 nm to 250 nm.
4 Characterization of Pickering Emulsion Drug Delivery Systems
Standard characterization assays include emulsion type identification, droplet size distribution, morphological observation (optical microscopy, transmission electron microscopy, scanning electron microscopy, laser scanning confocal microscopy), and in vitro stability evaluation (ambient storage monitoring, centrifugal testing, creaming assessment, droplet size and turbidity quantification) [13,16,19,22]. Targeted characterization workflows are additionally implemented based on intended clinical administration routes.
4.1 Transdermal Delivery Characterization
Dermal Pickering emulsions undergo comprehensive multi-dimensional evaluation:
- Rheological profiling: Assesses formulation suitability for topical cutaneous application.
- In vitro release testing: Primarily conducted using Franz diffusion cells. The high viscosity of Pickering emulsions prevents phase mixing under mild agitation, enabling periodic sampling of receptor medium to quantify cumulative drug release [9,18].
- Ex vivo transdermal permeation: Utilizes Franz diffusion cells with intact porcine skin as ex vivo epidermal barriers.
- Cutaneous drug distribution analysis: Post 24 h Franz diffusion testing, skin tissue is separated into stratum corneum, viable epidermis and dermis layers for drug quantification and distribution ratio calculation [17]. Alternately, Nile red-labeled emulsions are applied in permeation assays, with laser scanning confocal microscopy visualizing fluorescent drug localization within the stratum corneum, viable epidermis, dermis and hair follicles [15,16].
- Biosafety evaluation: In vitro MTT assays quantify viability of Df and HaCaT keratinocytes post emulsion exposure [12,17]; in vivo cutaneous irritation testing employs rabbit dorsal skin or human volunteer back skin models [12].
4.2 Oral Delivery Characterization
Research on oral Pickering emulsions remains limited, with standardized characterization covering three core dimensions:
- In vitro drug release profiling: Dialysis-based assays predominate for liquid oral formulations. Emulsions are sealed within dialysis bags/tubing immersed in simulated gastrointestinal media (pH 1.2 hydrochloric acid or pH 6.8 phosphate buffer), with orbital incubation at 37 °C and periodic sampling to quantify cumulative drug release [22,23]. Shao et al. [21] established an optimized assay directly mixing emulsions with simulated gastric fluid (pH 1.2 HCl containing 0.32% w/v pepsin and 0.2% w/v NaCl) or simulated intestinal fluid (pH 7.5 potassium phosphate buffer supplemented with 10 mg·mL⁻¹ bile salts and 2.4 mg·mL⁻¹ pancreatin). After 37 °C incubation, samples are centrifuged at 10,000 × g for 30 min to isolate clear aqueous supernatants for drug quantification and release rate calculation. This protocol recapitulates gastrointestinal pH and enzymatic environments while eliminating dialysis membrane interference for more physiologically relevant data.
- In vivo oral absorption pharmacokinetics: Rat intragastric administration generates pharmacokinetic parameters including peak plasma concentration (Cmax) and area under the curve (AUC) to quantify bioavailability enhancement [24,25].
- Pharmacodynamic assessment: Most investigations rely on in vitro cellular models, with only a minority incorporating in vivo animal disease models.
4.3 Injectable Delivery Characterization
Injectable Pickering emulsions constitute the most novel pharmaceutical application of Pickering systems, with limited published research demanding expanded characterization workflows. Xia et al. [26] characterized antigen-loaded PLGA nanoparticle-stabilized injectable emulsions by evaluating formulation flexibility, lateral mobility, biocompatibility and antigen encapsulation efficiency. Wood et al. [27] fabricated oseltamivir-loaded Pickering emulsions stabilized by glyceryl monostearate nanocrystals, implementing dialysis-based in vitro release assays to evaluate long-acting sustained release, WST-1 cellular proliferation tests to quantify anti-proliferative activity against human PANC-1 pancreatic cancer cells, and injectability testing using clinical needles of variable gauge sizes.
5 Future Perspectives
Growing research attention surrounds Pickering emulsion delivery systems, yet two major bottlenecks restrict their translational pharmaceutical deployment.
First, fundamental mechanistic questions governing emulsion fabrication require deeper elucidation. Solid particles constitute the core regulator of emulsion assembly and stability. Current literature quantifies particle wettability via particle-water-air three-phase contact angles, which deviate substantially from particle-oil-water interfacial wettability due to divergent physicochemical properties of air and oil media. For example, ferulic acid exhibits a 26.13° contact angle in air-water systems yet a 161.05° contact angle in Capmul C8-water mixtures [36]. Furthermore, contact angle measurements typically utilize micrometer-scale particles, whereas Pickering emulsions rely on nanoscale stabilizers. Nanoparticulation drastically alters intrinsic particle properties; whether such dimensional shifts modify three-phase contact angles remains uncharacterized, alongside standardized methodologies to quantify authentic oil-water interfacial wettability of emulsion nanoparticles. Discrepancies across studies evaluating particle charge and size effects likely arise from overlooked particle structural variables. Additionally, the regulatory roles of particle micromorphology and surface roughness remain insufficiently explored.
Second, existing Pickering emulsion research predominantly implements fragmentary in vitro characterization tailored to discrete experimental objectives, including ex vivo transdermal permeation, dialysis release testing and cellular cytotoxicity assays. Critical gaps persist in research tracking in vivo emulsion fate and biological mechanisms post-administration: gastrointestinal degradation of oral emulsions, plasma-mediated destabilization of injectable formulations, molecular drug release mechanisms, and systemic in vivo regulatory variables remain largely uninvestigated. Insufficient in vivo mechanistic data impedes translational development and clinical transformation of Pickering emulsion platforms.
Recent advances in novel oral and injectable Pickering emulsions demonstrate multifaceted pharmaceutical utility: these formulations mitigate surfactant-induced cutaneous irritation and amplify transdermal permeation for topical applications, elevate oral bioavailability of poorly soluble drugs to achieve sustained and targeted delivery (especially promising for innovative herbal oral dosage forms), and function as versatile carriers for next-generation immunological adjuvants, unlocking extensive translational potential across pharmaceutics. Systematic investigation of emulsion fabrication determinants, resolution of fundamental colloidal stability challenges, comprehensive mechanistic research on in vivo emulsion fate, and establishment of standardized correlative in vitro-in vivo characterization frameworks will lay robust theoretical and experimental foundations for developing clinical-grade Pickering emulsion drug delivery systems.