1 Introduction

During the past half a century’s developments of pharmaceutics, the polymers are increasingly demonstrated to be the backbone for supporting new kinds of drug delivery systems (DDSs) [1,2,3,4]. Initially, properties of polymers are successfully exploited to modify the drug release profiles for an effective, safe, and convenient therapeutic action [5,6,7]. For example, the insoluble and degradable polymers are frequently exploited to develop drug sustained or extended release through a diffusion mechanism in the formats of nanoparticles, nanofibers, and also bulk materials [8,9,10]. Hydrophilic and water-soluble polymers are always utilized to enhance the solubility and to accelerate the dissolution rates of poorly water-soluble drugs and also to develop the DDSs for providing the immediate or pulsatile drug release profiles [11,12,13]. However, how these DDSs show the desired functional performances has a close relationship with the drug-polymer co-existing status and the related materials engineering methods [14,15,16].

The drug presents in the polymer matrix mainly in the following formats: separate (such as depots in the inner section or nano crystals on the surface) [17, 18]; homogeneous distribution all over the polymeric carriers [19, 20]; and heterogeneous distributions (such as gradual distribution and discrete distribution) [21,22,23]. Among these co-existing manners, the most frequent type is the homogeneous distribution, by which the polymeric carriers’ properties are greatly exploited for the desired functional performances [24, 25]. These homogeneous products are often called polymer-based composites (as an opposite of hybrids, which often have separated phases within the subjects) or often solid dispersion in pharmaceutics [26,27,28]. How to make the drug molecules uniformly distribute all over the polymeric matrices comprises a big challenge to the researchers in the fields of pharmaceutics, materials science, nano science, and polymer engineering.

Electrospinning, as its peer electrospraying, is an electrohydrodynamic technique and initially a method for creating polymeric nanofibers [29,30,31,32]. The polymers that are applied for drug delivery and have fine electrospinnability are slightly over one hundred in literature [33, 34]. However, there are numerous polymer-based composites that are generated using electrospinning [35,36,37]. This contrast should have a close relationship with the capability of electrospinning in creating a wide variety of nanofibers with various loaded ingredients for functional applications. Initially, electrospinning is popular with the advent of this nano era due to a top-down, straightforward, and facile manner for creating nano products [38,39,40,41]. However, with the developments of this technique, its capability of generating nanofibers is fast expanded along several directions: (1) filament-forming polymers or some little molecules, typically lipid and β-cyclodextrin (CD), can be electrospun into nanofibers [42,43,44]; (2) the generation of multiple-chamber nanostructures in a single step using the multiple-fluid electrospinning, which is impossible for other top-down methods and also very difficult for most bottom-up methods such as molecular self-assembly [45, 46]; (3) the applications of materials without electrospinnability for producing nanofibers directly, i.e., working fluids without electrospinnability can be converted into nanofibers when they are treated simultaneously with electrospinnable polymer solution [47,48,49,50]; and (4) the applications of electrospun polymeric nanofibers as templates for creating other kinds of products, such as ceramics and other inorganic nanofibers from the after-treatment of the polymer-based nanofibers [51,52,53,54,55].

As for the multiple-fluid electrospinning and the related multiple-chamber structures, the most common one is coaxial electrospinning and its main products core-sheath nanofibers [56,57,58,59,60,61,62]. From the first reports about coaxial electrospinning [63], today there are 4356 publications (with “TS = coaxial electrospinning or core–shell nanofibers or core-sheath nanofibers” to search in Web of Science in 27-Jan-2022) about this processes and the corresponding core-sheath structures. Additionally, Dzenis once pointed out that coaxial electrospinning was one of the most important break points in this field [64]. What is more, along this way, tri-axial (abbreviation of tri-layer coaxial) and quad-axial electrospinning are successively reported in literature, and the related multi-layer core-sheath nanostructures were clearly demonstrated [25, 65,66,67,68,69]. However, a sharp contrast is that the investigations about side-by-side electrospinning and the related Janus nanofibers are extremely limited [70, 71]. The found literature in Web of Science is only 269 (with “TS = side-by-side electrospinning or Janus nanofibers” to search in Web of Science in 27-Jan-2022), and in which half of them are review papers. This has a close relationship with the difficulties of creating Janus nanofibers using two metal capillaries in a parallel manner as the spinneret. The same charge of two working fluids makes it inevitable that they separate from each other due to the repelling, when they are pumped out from the outlets of a spinneret nozzle. In turn, this phenomenon would result in the failure of creating Janus nanofibers with integrated side-by-side (or Janus) structures [72, 73].

To solve this issues, an eccentric spinneret was recently reported, which is characterized by two capillaries with one relied on the inner wall of another capillary [74, 75]. This spinneret is demonstrated to be effective for preventing the separation of two parallel working fluids due to the following reasons. One is that the two fluids were formed a full and whole circle for being charged, just as the concentric spinneret. The other is that the two working fluids can contact with each other through an enlarged surface area, not a point contact in the two-parallel metal capillary format. Later, this method was further improved by exploiting a third solvent to keep the drawing and drying processes simultaneously for creating Janus nanofibers with an integrated inner Janus structure [76, 77]. Inspired by this strategies and the related electrohydrodynamic knowledge, the parallel pumping of 3 or even 4 working fluids to the electrical fields should be possible for creating the 3-section Janus or even 4-section Janus nanofibers.

In this study, a brand-new tri-fluid electrospinning process is developed, which is characterized by a new structural spinneret. The electrospun tri-section Janus nanofibers (TJNs) contained helicide (a poorly water-soluble drug model), sodium dodecyl sulfate (SDS, a trans-membrane enhancer), and sucralose (a sweeter) in their owns’ polymer-based nanocomposites. The TJNs can be exploited for drug delivery through oral mucosa for realizing fast dissolution and rapid permeation for a therapeutic action, and meanwhile, a sequentially controlled release of them can ensure a convenient and compliant administration to the patients.

2 Materials and methods

2.1 Materials

Helicide (98% purity, 4-Formylphenyl beta-D-Allopyranoside) was received from Xi’an boliante Chemical Co., Ltd. (Xi’an, China). Two polymeric matrices of polyvinylpyrrolidone (PVP K 60, Mw = 360,000 and PVP K10, Mw = 8,000) were purchased from Sigma-Aldrich Corp. (Shanghai, China). Sodium dodecyl sulfate (SDS), N,N-dimethylacetamide (DMAc), anhydrous ethanol, methylene blue, and basic fuchsin were bought from Sinopharm group (Shanghai, China) and were used as received.

2.2 Preparation of TJNs

After some pre-experiments, three working fluids were prepared for implementing the tri-fluid side-by-side electrospinning to prepare the TJNs.

  • Fluid 1: 10.0 g PVP K60 and 4.0 g helicide were co-dissolved into 100 mL solvent mixture of ethanol and DMAc in a volume ratio of 7:3 (for optimizing the experimental conditions, 0.01 g methylene blue was added).

  • Fluid 2: 20.0 g PVP K10 and 10.0 g sucralose were co-dissolved into 100 mL ethanol (for optimizing the experimental conditions, 0.01 g basic fuchsin was added).

  • Fluid 3: 10.0 g PVP K60 and 0.5 g SDS were co-dissolved into 100 mL 80% (v/v) ethanol aqueous solution.

A homemade spinneret was developed to build a tri-fluid electrospinning system, which was explored for creating the TJNs. The fluid flow rates (mL/h) were fixed at 1.0:1.0:0.5 (Fluid 1:Fluid 2:Fluid 3). The applied voltage was fixed at 11.0 kV. The nanofiber deposition distance was fixed at 20 cm. The collected TJNs were kept at a vacuum drying oven for characterization.

2.3 Characterization of properties

2.3.1 Morphology and structure analyses

The morphology of electrospun TJNs was observed using a field emission scanning electron microscopy (SEM, FEI Quanta450FEG, USA). Their cross-sections were prepared by inserted a piece of TJNs into liquid nitrogen for 20 min and later broken manually. The samples for SEM were gold sputter-coated for 1.5 min under N2 atmosphere. The fibers’ diameters were estimated using ImageJ software (National Institutes of Health, USA) by analyzing over 100 fiber places in SEM images. The tri-section Janus structures of nanofibers were also assessed using a transmission electron microscope (TEM, JEM 2100F, JEOL, Tokyo, Japan).

2.3.2 State of the loaded components and their compatibility

An X-ray diffractometer (Bruker-AXS with Cu Kα radiation, Karlsruhe, Germany) was utilized for conducting X-ray diffraction (XRD) analyses. The experimental conditions: an applied voltage of 40 kV, a current of 30 mA, and a 2θ range from 5 to 60°. A Spectrum 100 FTIR Spectrometer (Perkin-Elmer, Billerica, USA) was exploited to implement the attenuated total reflectance-Fourier transform infrared (ATR-FTIR) measurements at a resolution of 2 cm−1 and at a range from 4000 to 500 cm−1.

2.4 Functional performances

2.4.1 Drug loading efficiency

The helicide concentration was measured using a UV–vis spectrophotometer (UV-2102PC, Unico Instrument Co., Ltd. Shanghai, China). The standard equation between the helicide concentration (C, μg/mL) and absorbance (A) was A = 0.117C-0.014 (R = 0.9996), which was built at the maximum absorbance at λmax = 270 nm and within a linear range of 0.0 to 25.0 μg/mL.

For determining the encapsulation efficiency (EE, %) of helicide in the TJNs from the tri-fluid electrospinning, an amount of 10.0 mg TJNs were dissolved into 500 mL distilled water. After detection of the solutions, the detected helicid content (CD) can be calculated from the standard equation, and the EE values can be achieved through Eq. (1):

$$EE=\frac{{C}_{D}}{{C}_{O}}\times 100\%$$
(1)

in which CO is a theoretical value according to the preparation conditions using Eq. (2):

$${C}_{\mathrm{O}}\%=\frac{{f}_{1}*{C}_{helicid}}{{f}_{1}*\left({C}_{helicid}+{C}_{PVP1}\right)+{f}_{2}*\left({C}_{sucralose}+{C}_{PVP2}\right)+{f}_{3}*\left({C}_{SDS}+{C}_{PVP3}\right)}$$
(2)

where f and C denote fluid flow rate and solute concentration, respectively; the subscript “1,”,”2,” and “3″ refer to the fluid number, respectively.

2.4.2 Fast disintegrating observations

In vitro dissolution and additional two self-created methods were explored to observe the fast disintegrating and fast-dissolving processes of the prepared TJNs. Those TJNs prepared during the optimization processes (i.e., containing blue and red markers) were exploited for distinguishing the sequential dissolution of encapsulated functional ingredients.

2.4.3 In vitro dissolution tests

In vitro dissolution tests were conducted according to the paddle method in Chinese Pharmacopoeia (2020 Ed.). An amount of 100.0 mg TJNs were immersed in 600 mL normal saline at 35 ± 0.5 °C. At predetermined time points, 5.0 mL aliquot was withdrawn, and 5.0 mL of fresh saline was added. The amounts of helicide released were measured and calculated. Experiments were repeated 3 times.

3 Results and discussion

3.1 The new tri-fluid electrospinning process

Among the four parts of an electrospinning system, i.e., power supply, collector, syringe pump, and spinneret, the spinneret is the most innovative one [78,79,80]. Often, a new spinneret can determine a new electrospinning process, for example, an eccentric spinneret for a side-by-side electrospinning [81] and a concentric spinneret for a coaxial electrospinning [82, 83]. In this study, a new spinneret is developed, whose information is concluded in Fig. 1. Figure 1a is a whole digital view of the spinneret, which has a weight of 37.2 g for easily installing the electrospinning system. Figure 1b shows the co-outlets of nozzle, with two outlets in a typical round shape and the third outlet in a “strange arch” shape. The inner arrangement of the metal capillaries and the combinations are disclosed in Fig. 1c. In the “strange arch” shape, a large contact surface area between the three working fluids can be ensured during the working processes for a successful preparation (as indicated by the letter “A”). The spinneret is very convenient for being fixed by one syringe pump, which the syringe holding the fluid passing through the “strange arch shape” can be directly inserted into the spinneret; the other two working fluids can be guided to the spinneret through the high elastic silicon tubes, as shown by the digital picture of Fig. 1d.

Fig. 1
figure 1

Construction of the structural spinneret: a a whole digital view; b the co-outlets of nozzle (the other “arch” was blocked by epoxy resin); c a diagram showing the inner arrangement of the metal capillaries and their combination using epoxy resin; d a digital picture telling the connections of spinneret with the three syringes holding the three sorts of working fluids

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Helicide is not soluble in water and ethanol but soluble in DMAc. SDS is soluble in water. Thus, although PVP is soluble in water and almost all the organic solvents, it is impossible for blending all the functional ingredients, helicide, SDS, and sucralose, with PVP to form a co-dissolving solution, and thus it is impossible to prepare a multiple-component nanocomposite using a single-fluid blending process. Multiple-fluid electrospinning has the capability of encapsulating multiple components from different working fluids. Here, to investigate the tri-fluid working process through the structural spinneret, color markers methylene blue and basic fuchsin were loaded into the co-dissolved working fluids of helicide-PVP K60 and sucralose-PVP K10, respectively. Only the fluid containing PVP K60 and SDS was transparent. The arrangements of three pumps for constructing the home-made electrospinning apparatus are shown in Fig. 2a. After optimizing the fluid flow rates of three working fluids, a droplet dripped from outlet of the spinneret’s nozzle can be observed in the up-right inset of Fig. 2a, showing the co-pumped out three fluids before applying the high voltage for preparing TJNs. The ways that the three working fluids were guided into the spinneret and the connection between the power supply and the spinneret through an alligator clip are shown in the digital photo of Fig. 2b. When the applied voltage was lifted to 15 kV, the electrospinning process is stable. A typical working process was observed in Fig. 2c. The platitudes are a compound Taylor cone, followed by a straight fluid line and an instable region, characterized by the gradually enlarged bending and whipping circles. An enlarged image of the compound Taylor cone is given in Fig. 2d. The two colors (blue and red) and a transparent section in the cone demonstrated the co-electrospinning of the three working fluids.

Fig. 2
figure 2

Implementation of the tri-fluid electrospinning processes: a a digital image of the home-made electrospinning apparatus, the up-right inset shows a droplet from the nozzle of spinneret before applying the high voltage; b the ways that the three working fluids were led into the spinneret and the connection between the power supply and the spinneret through an alligator clip; c a typical working process with bending and whipping loops; d a typical compound Taylor cone with color markers

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As mentioned previously, the publications about coaxial electrospinning and core-sheath nanofibers are greatly larger than their counterparts, i.e., side-by-side electrospinning and Janus nanofibers. Similarly, the investigations about tri-axial electrospinning and tri-layer core-sheath nanofibers are reported in decades of papers, but few articles can be found about the tri-fluid side-by-side electrospinning and tri-layer Janus nanofibers. The key difficult point is that it is very hard to keep the side-by-side working fluids to be drawn in an integrated manner through the Taylor cone, straight fluid jet, and bending and whipping processes [84, 85]. When these fluids are pumped out from the nozzles, they carry the same electrical charges and thus it is inevitable to repel each other using a traditional spinneret comprising three parallel metal capillaries (diagrammed in Fig. 3). Particularly, the charges distribute in an irregular format. These adverse factors would make the formation of integrated TJNs failure due to separation of each sections during the electrospinning processes.

Fig. 3
figure 3

The formation mechanism of the electrospun TJNs using the new spinneret

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In obvious contrast, the present new spinneret has its advantages to ensure a robust and effective preparation of TJNs. First of all, the three fluids have a larger contact surface area (as indicated by “A” in Fig. 1). Second, the working fluids can be more easily self-regulated into a round shape due to surface tension although an irregular shape of the outlet of nozzle (as indicated by letter “A” in Fig. 3). Third, the spinneret is coated mostly by epoxy resin, leaving only a small section of metal capillary for connecting the alligator clip, which is favorite for an effective transferring of the electrical energy to the working fluid, other than being scattering to the environment [86].

3.2 The TJNs’ morphologies and inner structures

The surface morphologies of the electrospun TJNs are shown in Fig. 4a, with an enlarge image in its up-right inset. The estimated diameters of these nanofibers are about 870 ± 140 nm (Fig. 4b). Clearly, there TJNs are round and in a straight line format with smooth surface. Although unspinnable fluid of PVP K10-sucralose was exploited, the electrospinnable PVP K60-helicide and PVP K60-SDS fluids were able to ensure the formation of linear nanofibers without beads or spindles. The cross-sections of TJNs are shown in Fig. 4c and d. It is obvious that three different sections (labeled with “A,” “B,” “C” beside) within the cross-section of nanofiber can be discerned.

Fig. 4
figure 4

Morphologies of the prepared tri-section Janus nanohybrids: a the surface morphology of the nanofibers, the up-right inset shows an enlarged image; b the nanofibers’ diameters and their size distribution; c the cross-sections of the tri-section nanofibers; d a typical image of the nanofiber’s cross-section, in which, “A”(sucralose-PVP 10), “B”(helicide-PVP K60), “C” (SDS-PVP K60), three different sections can be clearly discerned

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TEM images of the TJNs are shown in Fig. 5a to c. The gray levels in the TEM images taken under bright field are often from three aspects, i.e., element, thickness, and density. When the magnification is 5,000, all the nanofibers showed the same gray levels, which is shown in Fig. 5a. However, when the magnification is enlarged to 200,000, the different gray levels within the TJNs can be clearly distinguished out, as exhibited in Fig. 5b and c. The multiple gray levels should have a close relationship with the view angle on the nanofibers. A diagram showing the formations of different regions with various gray levels is drawn in Fig. 5d. The thicker and the more sections involved, the darker the gray level is.

Fig. 5
figure 5

Inner structures of the prepared TJNs: a a whole TEM image of the nanofibers on the carbon membrane; b and c two typical TEM images; d a diagram showing the formations of different regions with various gray levels

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3.3 The three sections of polymer-based nanocomposites within the TJNs

Essentially, electrospinning is a physical method, which electrostatic energy is exploited to eliminate the solvents from the working fluids at an extremely short time period, often at a scale of several decades of milliseconds [87,88,89]. Based on this situation, it is often anticipated that the physical state of components in the liquid working fluids will be propagated into the solid nanofibers. This advantage makes electrospinning a highly popular tool for preparing drug-polymer composites or molecular solid dispersion in pharmaceutical field [34, 90, 91]. Thus, there are numerous nanofiber-based composites or solid dispersion in literature, which are often fabricated using a single-fluid blending electrospinning process [20, 92, 93]. The active ingredient, the filament-forming polymer, and sometimes other additives are all co-dissolved into one electrospinnable working fluid, and then the fluid was transferred into polymer-based composites.

However, these homogeneous polymer-based composites and also the single-fluid blending electrospinning are only limited to some special situations, in which the drug, the polymer, and also the additive can be co-dissolved together in a solvent or a solvent mixture. Meanwhile, the single solvent system must ensure that the polymer has fine electrospinnability and must ensure that the drug and additives have enough loading for functional performances. Thus, multiple-fluid electrospinning processes and the related complex nanostructures are able to expand the capability of electrospinning in generating functional nanomaterials. Here, the tri-fluid side-by-side electrospinning processes have exploited three different kinds of solvent systems, i.e., ethanol and DMAc for PVP K60 and helicide, ethanol for PVP K30 and sucralose, and ethanol and water for PVP K60 and SDS. All the solutions were transparent liquids. After electrospinning, the TJNs’ XRD patterns were achieved (Fig. 6). Compared with the XRD patterns of the raw helicide, sucralose, and SDS, in which Bragg sharp peaks suggesting crystalline materials, there are no any sharp peaks on the curve of TJNs, but two halos like the XRD patterns of PVP K10 and K60. These phenomena gives a hint that all the crystalline helicide, SDS, and sucralose have been transferred into amorphous polymer-based composites in their owns’ sections of tri-section Janus products, whereas the whole TJNs are nanohybrids, which consist of three different sorts of polymer-based nanocomposites.

Fig. 6
figure 6

XRD patterns of the tri-section TJNs and the five raw materials including PVP K60 and K10, SDS, sucralose, and helicide

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In this study, three different functional ingredients were successfully encapsulated into two different polymeric matrices to create the designed TJNs. Their molecular formula are concluded in Fig. 7. Although the polymer matrices PVP K10 and K60 have their differences in molecular weights and dissolution rates, they similarly have numerous C = O groups in their molecules and meanwhile the N bring some positive charges. Both helicide and sucralose have OH groups in their molecules. Thus, it can be anticipated that both of them have fine compatibility with PVP. This is because the favorite secondary interaction, i.e., hydrogen bonding, can be formed between them, which can keep a high stability of the composites through a long time period [11]. SDS, as a trans-membrane enhancer, has negative charges on the element O; thus, electrostatic actions can form between SDS and PVP, i.e., PVP-SDS nanocomposites also have a high stability. Thus, it is no strange that all the sharp peaks presented in the figure regions of the ATR-FTIR spectra of sucralose, SDS, and helicide have disappeared in the spectra of TJNs due to the secondary interactions, which have revised their covalent bonds’ original stretching and bending actions. Meanwhile, compared with the spectra of PVP K10 and K60, the characteristic peak places of C = O of TJNs have showed some red shifts from 1662 to 1657 cm−1.

Fig. 7
figure 7

ATR-FTIR spectra of the TJNs and the five raw materials including PVP K60 and K10, SDS, sucralose, and helicide, and their molecular formula

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3.4 The functional performances of the prepared TJNs

The measured content of helicide in the TJNs was 8.23 ± 0.41%. According to the experimental conditions, the theoretical concentration is 8.12%. Thus, the drug loading efficiency is 101.4%. This result suggests that there were no any drug losing during the electrospinning process. All the drugs have been encapsulated into the TJNs due to just a fast drying procedure of the co-dissolving solutions, which is similar as all the other electrospinning processes.

Three different methods are developed for measuring the fast dissolution properties of the electrospun TJNs and disclosing the sequential release performances. Shown in Fig. 8, a disintegration experiment was carried out using a piece of glass slide. After about 10 min of the depositions of TJNs, a drop of water was dripped on the TJNs. A camera was exploited to record the fast disintegrating process. After contacting the water, the TJNs were quickly disintegrated into transparent gels, as demonstrated by the gradually enlarged circle from 1 to 6 in Fig. 8. The total time was 4 s for the buried characters “USST” (abbreviation of University of Shanghai for Science and Technology) to be completely appeared.

Fig. 8
figure 8

A glass slide was used to collect TJNs to test the fast disintegrating processes, the time cost from 1 to 6 was 4 s

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For drug delivery, the drug release is most frequently measured using the quantitative methods, particularly those dosages form for drug sustained release [22]. The above-mentioned fast disintegrating experiment was just a qualitative observation. According to Chinese Pharmacopoeia (2020 Ed.), the paddle method was used to measure the dissolution of helicide. As the SDS and sucralose have no any absorbance at the maximum wavelength of λmax = 270 for helicide. Thus, the absorbance of dissolution media were detected, and the values were exploited to calculate the drug concentration using the standard equation. The result is shown in Fig. 9. As anticipated, all the loaded helicide in the TJNs was freed within 1 min. In comparison, the helicide powders (≤ 50 μm) released only 3.6 ± 1.4% into the dissolution media after a time period of 30 min, suggesting a typical poorly water-soluble drug.

Fig. 9
figure 9

The in vitro dissolution test results of the TJNs and raw helicide powders

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The TJNs prepared during the optimization of experimental parameters (i.e., with color markers) were exploited to distinguish the dissolution procedures of different functional ingredients encapsulated in the TJNs. Shown in Fig. 10, a piece of TJNs were placed on a cup of water with a stirring rate of 50 rpm. The whole time from 1 to 6 was 34 s. During the processes, two phenomena were clear, one is that the center of the floated solid TJNs (in the shape of “T” due to the stirring) was mainly in purple and blue colors, whereas the dissolution medium was in pink color, suggesting that the red marker dissolved and diffused to the dissolution media faster than the blue marker. Both of the red and blue markers have fine water solubility, and both of them contacted the environments due to the Janus structures. Thus, it is the solubility differences of their polymeric matrices, i.e., PVP K10 and PVP K60, that made the two colors be released through different rates through the polymeric erosion mechanisms. The other is that the water gradually turned its color from pink to purple, also suggested that the later dissolution and diffusion of blue marker. These phenomena suggest that the sucralose loaded with PVP K10 will be faster released than the drug helicide encapsulated with PVP K60. Thus, in the administration applications, the sweet taste of sucralose will be firstly felt by the patients and will mask the bitterness of helicide, and thus the patients’ compliance can be effectively improved by this sequential release performance.

Fig. 10
figure 10

A disintegrating release experiment for measuring the dissolution procedure of functional ingredients within the TJNs by using the color markers

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Helicide is a monomer extracted from the fruit of wild plant radish tree of Longan family [94]. It is frequently used for neurasthenia, neurasthenia syndrome, and vascular nerve headache. However, its poor water solubility has greatly limited its applications, and its bitter taste has decreased its patient compliance [95]. Here, it was selected as a model active pharmaceutical ingredient to develop a nanofiber-based DDS. It is expected that the suggested protocols can be applied to many other drugs due to the strategies and mechanisms disclosed here. Shown in the diagram of Fig. 11, the TJNs have three sections in an irregular side-by-side manner. All the three sections contact the environments. The side from the “arch shape” outlet of spinneret has the thinnest thickness and largest surface, which can also play a role in making a different dissolution rate besides the polymeric matrices, although this point cannot be detected presently due to the extremely fast whole dissolution rate. The release of SDS in an earlier step can benefit an effective trans membrane of the later released drug molecules. Meanwhile, the release of sucralose will be rapider than the helicide for a better compliance, as detected in the above-mentioned experiments. Thus, the whole sequential release of SDS, sucralose, and helicide from their owns’ PVP-based nanocomposites will ensure the tri-section Janus medicated hybrids an ideal nano DDS for the patients.

Fig. 11
figure 11

Sequential release of sucralose, SDS, and helicide from the prepared TJNs

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In the traditional electrospun fast disintegrating membranes, orodispersible films, and sublingual membranes, the drug and also the additive are simultaneously dissolved [47]. Here, the TJNs not only release the loaded functional ingredients in an immediate manner, but during the fast process, the release of different ingredients can be manipulated in a certain order. For drug delivery applications, this is favorite for the patients; the formerly release of sweeter and trans-membrane enhancer can effectively cover up the bite taste of drug and promote drug transportation to penetrate the biological mucosa due to an earlier release than drug and thus increase the conveniences, compliance, and effectiveness of drug delivery to the patients. This strategy, on one hand, should be not only useful for the delivery of a certain drug but should be more useful for manipulating the combined therapy of several different kinds of drugs, which are presently under investigations. On the other hand, with the hints from literature [96,97,98]. The protocols can be explored for developing a series of multifunctional hybrid and composite materials in other scientific fields such as food and agroforestry.

4 Conclusions

A new tri-fluid electrospinning, characterized by a homemade spinneret, was successfully developed for preparing tri-section Janus nano structures. Three functional ingredients, sucralose, SDS, and helicide were loaded separated into the Janus structures with two different polymeric matrices, i.e., PVP K10 and PVP K60. The prepared TJNs were demonstrated to have a linear morphology and comprise three nanocomposites, i.e., helicide-PVP K60, SDS-PVP K60, and sucralose-PVP K10, which are demonstrated by SEM and TEM images. XRD and ATR-FTIR verified that the functional ingredients, helicide, SDS, and sucralose, existed in their own sections in an amorphous state due to the favorite secondary interactions with the PVP matrices. Two disintegrating experiments (with a drop of water and a cup of water) and in vitro dissolution tests demonstrate that the TJNs have the fast dissolution performances, and meanwhile, they can manipulate the sucralose, SDS, and helicide to be released in a sequential manner. This is useful for compliance (sweeter masking the bite taste of helicide) and effective (SDS as trans-membrane enhancer) drug delivery. The tri-fluid electrospinning and the TJNs reported here pave a new way for developing multiple functional nanomaterials.