In vitro drug controlled-release behavior of an electrospun modified poly(lactic acid)/bacitracin drug delivery system

Abstract

Poly(lactic acid-co-lysine) (PLL) was applied as a modified material to improve the hydrophilicity, reactivity, and degradation rate of poly(L-lactic acid) (PLLA). In the drug delivery system, PLLA and PLLA/PLL were selected as the carrier materials of drug-loaded fibers, and bacitracin (BAC) as the sustained release drug. Uniaxial drug-loaded fibers (PLLA/BAC, PLLA/PLL/BAC) and coaxial drug-loaded fibers ((PLLA/PLL/BAC)-PLLA, (PLLA/BAC)-(PLLA/PLL)) were prepared using electrospinning. The chemical structures and thermal properties of the electrospun drug-loaded fibers were analyzed using Infrared Spectroscopy (IR) and Differential Scanning Colorimetry (DSC) separately and an Ultraviolet spectrophotometer (UV) was used to characterize the extracorporeal drug releasing behavior. The results indicated that the main interaction between the BAC and carrier materials such as PLLA and PLLA/PLL was physical force; the uniaxial drug-loaded fibers with uniform diameters showed a higher release rate compared with the coaxial drug-loaded fibers owing to the protection of shell materials in the coaxial fibers. The drug release rate of the drug-loaded fibers increased due to the addition of hydrophilic PLL; the drug release mechanism in both the uniaxial and coaxial drug delivery systems could be interpreted by a biexponential-biphase kinetics function. Two kinds of fibers with different drug release patterns could be fabricated by uniaxial and coaxial electrospinning. Drug in uniaxial fibers could be quickly released and was suitable for antibiotic treatment while the release of drug in coaxial fibers was a kind of controlled release which could be applied for a drug delivery system of long-term and small doses.

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Introduction

Poly(L-lactic acid) (PLLA) is a kind of biomedical polymer material and has become the most attractive medical biological material on account of its excellent biocompatibility, appropriate biodegradability and metabolism of its degradation products.^1–3 Poly(lactic acid-co-lysine) (PLL) copolymerized by L-lactic acid and L-lysine possesses excellent biocompatibility, certain reactive activity, good hydrophilicity and a short degradation cycle. The blends of PLLA/PLL have different degradation periods, functional groups, good hydrophilicity, and favourable medical and processing properties, so they can be utilized in tissue engineering and drug delivery systems.⁴ The drug-loaded nano-fibers obtained using electrospinning with a large surface area and high porosity have been widely applied in the fields of the local release of drugs and wound cures, especially as a postoperative gauze to protect the skin tissue from being infected by bacteria.^5–10 Therefore, PLLA and its composite materials present broad prospects for drug release.¹¹ Fibers with a core–shell structure where medicine can be introduced into the core layers, and shell materials can be prepared using coaxial electrospinning technology and play the role of a barrier, can form a drug delivery system just like a repository.^12,13 Drug in the delivery system is released sustainedly with the continuous degradation of the shell materials so as to maintain an effective concentration of medicine in the blood and minimize side-effects.¹⁴

Bacitracin (BAC) is a kind of peptide antibody, which is a strong antibiotic, whose antibacterial spectrum is similar to penicillin. BAC can strongly inhibit Gram-positive bacteria and is mainly used for staphylococcal infections and topical skin infections.¹⁵ In this study, BAC was employed as a sustained release drug, and the uniaxial drug-loaded fibers (PLLA/BAC, PLLA/PLL/BAC) and coaxial drug-loaded fibers ((PLLA/PLL/BAC)-PLLA, (PLLA/BAC)-(PLLA/PLL)) were fabricated using electrospinning. Infrared Spectroscopy (IR) and Differential Scanning Colorimetry (DSC) were applied to characterize the chemical structures and thermal properties of the electrospun drug-loaded fibers. The mass loss of the drug-loaded fibers was evaluated and a UV spectrophotometer was used to investigate the in vitro drug releasing behavior of the different drug-loaded fibers.

Experimental

Materials

PLLA, at a molecular weight (M_w) of 3.05 × 105 g mol⁻¹, was purchased; PLL, M_w of 1.98 × 10⁴ g mol⁻¹, was lab-made; N,N-dimethyl formamide (DMF) and dichloroethane (DCE), analytical reagents, were purchased; phosphate buffered saline (PBS) was purchased; BAC, was purchased from Aladdin (Shanghai) Industrial Corporation.

Preparation of electrospun fibers

9 wt% of PLLA, PLLA/BAC, PLLA/BAC and PLLA/PLL/BAC were prepared by dissolving PLLA, PLLA/PLL, PLLA/BAC and PLLA/BAC/BAC in DCE and DMF (DCE : DMF = 9 : 1, wt%). The content of BAC in the solute was 9 wt% in the uniaxial drug-loaded fibers and the content of BAC in the core layer was 15 wt%. Then the solutions were stirred in sealed containers for 24 h and dispersed for 0.5 h using ultrasonication. Subsequently, uniaxial drug-loaded fibers (PLLA/BAC, PLLA/PLL/BAC) and coaxial drug-loaded fibers ((PLLA/PLL/BAC)-PLLA, (PLLA/BAC)-(PLLA/PLL)) were fabricated using an SS-2554 Electrospinning Set (UCALERY BEIJING CO., Ltd). (A)–(B) fibers stand for (core)–(shell) coaxial fibers.

Characterization

A Scanning Electron Microscope (SEM) from TESCAN. Ltd., Czech Republic (VEGA 3 LMH) was used to investigate the surface and cross-section morphology of the drug-loaded fibers, and the average fiber diameter and the standard deviation were determined by taking at least 50 measurements for each image using Image J software.

In order to evaluate the thermal properties such as T_g, T_c, T_m and Cr_PLLA of the electrospun fibers, it was necessary to use a Differential Scanning Calorimeter (DSC) from METTLER TOLEDO. Ltd. (Switzerland) with a heating rate of 10 °C min⁻¹ from 0 °C to 200 °C under nitrogen. The crystallinity of the spinning fibers was calculated according to the melting heat of the heating DSC curve by eqn (1), and the PLLA crystallinity of the fibers was calculated according to eqn (2). Wherein Cr is the crystallinity of the spinning fiber, Cr_PLLA is the crystallinity of PLLA, ΔH⁰_f is the heat of melting of the complete crystallization of PLLA and its value is −93.7 J g⁻¹. ΔH_f is the melting heat of spinning fibers and w_PLLA is the PLLA content (wt%) in the drug-loaded fibers.

Cr = (ΔH_f/ΔH⁰_f) × 100% (1)

Cr_PLLA = (ΔH_f/ΔH⁰_f)/w_PLLA × 100% (2)

The chemical structures of the drug-loaded fibers were analyzed using Fourier Transform Infrared Spectroscopy (FT-IR) with an instrument from Thermo Scientific. Ltd., US (Nicolet iS10). The superfine fibers were dissolved in DCE, then the solutions were coated on the surface of potassium chloride tablets. After the solvents were volatilized thoroughly, the samples were scanned in the wave number range of 4000 cm⁻¹ to 400 cm⁻¹.

The extracorporeal drug releasing behavior was analysed using a UV spectrophotometer (UV-2550) from SHIMADZU. Ltd., Japan. Different concentrations of BAC were dissolved in PBS (pH 7.4). The characteristic absorption peak of 254 nm could be defined in the UV absorbance curve. Then the fitting equation (eqn (3)) could be obtained using the linear regression of the different BAC concentrations and absorbance values. The concentration of BAC could be calculated by measuring the absorbance value (A) of the drug-loaded fiber near 254 nm with the UV spectrophotometer, and the cumulative release rate could be calculated from eqn (3).

C (mg L⁻¹) = −10.68 + 597Abs (3)

In the equation, C is the concentration of BAC, and Abs is the absorbance value.

The equation of cumulative drug release rate and drug release time was fitted by the biexponential-biphase kinetics function eqn (4),^16–18 wherein M_t and M_∞ are the drug release doses after drug releasing for t h and the total drug-loaded amount, respectively. α and β are drug release rate constants, and Q₀ is the initial drug concentration in the buffer solvent. The equation consists of fast and slow phases, namely the impact and slow-release phases, and the impact phase indicates the sudden release effect at the outset, while the slow-release phase expresses the subsequent controlled release.

The degradation properties of the drug-loaded fibers were analyzed using a water bath at 37.2 °C. The mass loss rate of the fibers could be calculated using eqn (5) in which W₀ and W₁ are the mass of the fibers before and after degradation, respectively.

Mass loss rate = (W₀ − W₁)/W₀ × 100% (5)

Results and discussion

Surface morphology of the drug-loaded fibers

The PLLA/BAC fibers, PLLA/PLL/BAC fibers, (PLLA/PLL/BAC)-PLLA fibers and (PLLA/BAC)-(PLLA/PLL) fibers were obtained with the parameters as shown in Table 1.

Table 1 The parameters of the electrospun fibers^a

Drug-loaded fibers	PLLA/BAC	PLLA/PLL/BAC	(PLLA/BAC)-(PLLA/PLL)	(PLLA/PLL/BAC)-PLLA
a Notes: ^×, * are the values of the core and shell solutions, respectively.
Concentration of solutions/wt%	9	9	9^×, 9*	9^×, 9*
Voltage/kV	18	18	24	24
Collecting distance/cm	13	13	15	15
Feed rate/mL min^−1	0.02	0.02	0.01^×, 0.02*	0.01^×, 0.02*
Drug-loaded amount/wt%	9	9	5	5

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The following conclusions could be drawn from the SEM micrographs of the drug-loaded fibers shown in Fig. 1. The fibers’ surfaces were smooth and the morphologies were neat. There were no BAC particles on the fibers’ surfaces which demonstrated that they functioned well as carrier materials. Due to the core–shell structure of the coaxial fibers and the larger diameter of the coaxial spinning needle compared to that of the uniaxial spinning needle, the average diameter of the uniaxial drug-loaded fibers was smaller than that of the coaxial drug-loaded fibers. Since the addition of PLL with a low relative molecular weight reduced the electrospinning solution viscosity and the reactive groups of PLL improved the conductivity of the spinning solution, the average diameter and standard deviation of the PLLA/PLL/BAC fibers were much smaller than those of the PLLA/BAC fibers, allowing the spinning solution to be drawn and stretched easily. The average diameter of the (PLLA/BAC)-(PLLA/PLL) fibers was smaller than that of the (PLLA/PLL/BAC)-PLLA fibers, which could be attributed to the faster feed rate of shell materials than that of core materials in the spinning process. Therefore, there was a higher content of PLL in the (PLLA/BAC)-(PLLA/PLL) fibers, resulting in fibers with finer diameters and a wider diameter distribution.

Fig. 1 SEM micrographs of the drug-loaded fibers and average diameters (a) PLLA/BAC (Φ 1634 ± 192.6 nm); (b) PLLA/PLL/BAC (Φ 1465 ± 216.3 nm); (c) (PLLA/PLL/BAC)-PLLA (Φ 1852 ± 201.4 nm); (d) (PLLA/BAC)-(PLLA/PLL) (Φ 1826 ± 208.5 nm).

Chemical structure analysis of the drug-loaded fibers

The FT-IR spectra of BAC, PLLA/BAC, PLLA/PLL/BAC, (PLLA/BAC)-(PLLA/PLL), and (PLLA/PLL/BAC)-PLLA fibers are shown in Fig. 2.

Fig. 2 FT-IR spectra of BAC and BAC-loaded fibers (a) BAC; (b) PLLA/BAC; (c) PLLA/PLL/BAC; (d) (PLLA/PLL/BAC)-PLLA. (e) (PLLA/BAC)-(PLLA/PLL).

The common characteristic absorption peaks of the PLLA fibers and PLLA/PLL fibers in the infrared spectrum were 1900–1650 cm⁻¹ (stretching vibration of C=O), and 1300–1000 cm⁻¹ (stretching vibration of C–O and framework vibration of C–C). There were two acute peaks at 3540–3180 cm⁻¹ on account of the NH₂ and NH in PLL.

In the FT-IR spectra, the specific absorption peaks (1746 cm⁻¹, 1092 cm⁻¹) of PLLA and PLLA/PLL didn’t disappear with no obvious deviation. The main chemical groups of BAC are C=O, C=N, NH₂, NH, –OH and C–S. The peak superposition of the partial functional groups of PLLA, PLL and BAC occurred because of their same groups. The strength of the characteristic absorption peaks (3244 cm⁻¹, 1651 cm⁻¹, and 1539 cm⁻¹) of BAC decreased significantly, which indicated that the interaction of BAC with the carrier materials was physical and the addition of BAC into PLLA and PLLA/PLL did not change their chemical structures.

Thermal and crystallization properties of electrospun fibers

Fig. 3 shows the DSC curves of the PLLA/BAC fibers, PLLA/PLL/BAC fibers, (PLLA/PLL/BAC)-PLLA fibers and (PLLA/BAC)-(PLLA/PLL) fibers, and the analysis of the crystallization and thermal properties are summarized in Table 2.

Fig. 3 DSC curves of BAC-loaded fibers (a) PLLA/BAC; (b) PLLA/PLL/BAC; (c) (PLLA/PLL/BAC)-PLLA; (d) (PLLA/BAC)-(PLLA/PLL).

Table 2 Crystallization and thermal properties of BAC-loaded fibers^a

Crystallization and Thermal properties	Tg/°C	Tc/°C	Tm/°C	CrPLLA/%
a Tg is the glass transition temperature; Tc is the cold crystallization temperature; Tm is the melting temperature.
PLLA/BAC	62.5	85.1	167.2	43.5
PLLA/PLL/BAC	58.8	77.2	163.1	44.0
(PLLA/PLL/BAC)-PLLA	61.8	84.6	166.7	42.9
(PLLA/BAC)-(PLLA/PLL)	61.0	82.3	166.1	42.4
PLLA/PLL	56.5	75.8	162.9	44.2
PLLA	63.3	87.3	169.6	42.1

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The addition of PLL and BAC could affect the thermal and crystallization properties of the PLLA fibers. PLL played the role of a diluent. On the one hand, it provided an active environment for the chain segments of the PLLA, lowered the internal rotation resistance between the PLLA chains, and promoted the regularity of the PLLA molecular chains. Consequently, the T_g of the modified PLLA fibers declined and the crystallinity increased. On the other hand, the dilution effect could increase the adjacent distance of the PLLA intermolecular chains, weaken the entanglement of the PLLA molecules, decrease the intermolecular force and make it difficult to grow into a wafer and crystal. Thus, the T_g and crystallinity of the PLLA in the modified PLLA fibers declined.

BAC was not soluble in the spinning solution. BAC could improve the crystallinity of the PLLA owing to its role as a nucleating agent. Nevertheless, it could impede the movement of the PLLA molecular chains. The addition of BAC improved the crystallinity of the PLLA because the nucleation of BAC was a stronger effect in the electrospinning process than impediment at room temperature. In addition, high density amines and imines in PLL and BAC could form hydrogen bonds with the carbonyl group of PLLA, which reduced the interaction between the PLLA molecular chains and resulted in the T_g increase and the crystallinity decline of the PLLA.

The T_g values of the PLLA/BAC fibers, PLLA/PLL/BAC fibers, (PLLA/PLL/BAC)-PLLA fibers and (PLLA/BAC)-(PLLA/PLL) fibers were lower than those of the PLLA fibers and PLLA/PLL fibers under the mutual effects of factors described above, among which the dilution effect of the PLL had an obvious effect. The crystallinity increased due to the mutual influence of the dilution and nucleation caused by the BAC.

There appeared obvious cold crystallization peaks in the DSC heating curve of the modified PLLA electrospun fibers, and T_c had a sharp decline compared with the neat PLLA fibers. The cold crystallization peak temperature of the PLLA resin of M_w 359 × 10³ is 122.4 °C.¹⁹ However, the T_c of the PLLA fibers and modified PLLA fibers reduced to 72–88 °C because the effect of the electrospinning charge led to the stretching of the PLLA chains and the formation of an α′ crystal structure with a weak stability. The α′ crystal structure converted into a more stable α crystal structure along with the temperature increase in the DSC test. The reason why the T_c of the PLLA/PLL fibers was lower than that of the PLLA fibers was that the dilution effect of the PLL was conducive to the formation of crystals in the electrospinning process for the PLLA molecular chains. The hydrogen bond formed between the amines and imines of the PLL and BAC with the carbonyl of the PLLA in the modified fibers decreased the molecular chain flexibility, so the stability of the crystal declined due to the difficult molecular chain movement, which decreased the T_c. In contrast, BAC had little effect on the cold crystallization temperature of the PLLA in the modified fibers.

The drug releasing behavior in vitro

The drug release curves of the PLLA/BAC fibers, PLLA/PLL/BAC fibers, (PLLA/BAC)-(PLLA/PLL) fibers and (PLLA/PLL/BAC)-PLLA fibers are shown in Fig. 4.

Fig. 4 Drug release curves of drug-loaded fibers (a) PLLA/PLL/BAC; (b) PLLA/BAC; (c) (PLLA/BAC)-(PLLA/PLL); (d) (PLLA/PLL/BAC)-PLLA.

The uniaxial drug-loaded fibers had faster drug release rates than the coaxial drug-loaded fibers did because of the homogeneous mixing drug delivery system of the uniaxial drug-loaded fibers. The uniaxial drug-loaded fibers had a higher drug content and exhibited concentration gradients in PBS, so the drug release behaviors conformed to a drug diffusion mechanism. However, the coaxial fibers belonged to a storage reservoir drug delivery system, and their main release rates depended on the shell corrosion and degradation of the PLLA and PLLA/PLL because of the protection from the shell materials.

The PLLA/PLL/BAC fibers showed a faster drug release rate than the PLLA/BAC fibers due to the content of the hydrophilic PLL which was more easily infiltrated by PBS and broke away from the fibers quickly. The drug release rate of the (PLLA/BAC)-(PLLA/PLL) fibers was faster than that of the (PLLA/PLL/BAC)-PLLA fibers. The PLLA/PLL of the shell material was more easily corroded than the PLLA, so the (PLLA/BAC)-(PLLA/PLL) fibers showed a faster drug release rate. The encapsulation of the dense PLLA protected BAC from totally diffusing from the fibers, leading to incomplete drug release with the cumulative release amount being less than 95% in 16 days.

The mass loss of the BAC-loaded fibers within a degradation period of 16 days can be seen in Fig. 5. The reasons for the mass loss of the fibers included the drug release and the degradation of the carrier material. The uniaxial fibers with the larger specific surface areas degraded faster than the coaxial fibers and the drug in the uniaxial fibers was inclined to be released. Thus, the mass-loss rates of the uniaxial drug-loaded fibers were faster than those of the coaxial drug-loaded fibers. The addition of the hydrophilic PLL in the carrier promoted the erosion and degradation which could increase the drug release and the degradation of the carrier material. The mass loss was based on the drug release at the beginning of five days, and the subsequent mass loss was mainly attributed to the degradation of the carrier material.

Fig. 5 The mass loss of BAC-loaded fibers in a 16 day period (a) PLLA/PLL/BAC; (b) PLLA/BAC; (c) (PLLA/BAC)-(PLLA/PLL); (d) (PLLA/PLL/BAC)-PLLA.

Schematic diagrams of the coaxial electrospinning fibers are shown in Fig. 6. The Taylor cone is stretched and the fibers are formed with the function of the electric field at the coaxial needle. Splitting theories²⁰ have indicated that the Taylor cone can be further split to form finer fibers during the movement towards the receiver under the high electric field force. The fibers could form four different types in the coaxial electrospinning process with the splitting of Taylor cone, and the profile and cross-sectional schematic diagrams of the coaxial spun fibers are also shown in Fig. 6.

Fig. 6 Schematic diagrams of the electrospinning process of the coaxial fibers. A, B, C and D are four different types of fiber.

In Fig. 6, A displays that part of the core–shell coaxial fibers is split under the high voltage, and there appear bistratal drug-loaded materials where the core drug is exposed outside. The drug release rate of the fibers is faster than that of the coaxial fibers but slower than that of the uniaxial fibers. B demonstrates that the drug is completely encapsulated into the core material and the drug release is controlled by the shell materials. C indicates the existence of the core materials alone with drug in the fiber because of the split. D represents the fibers which merely have the shell materials.

According to research to date,²¹ the release of the drug in a hydrophobic carrier material is influenced by both the diffusion mechanism and corrosion degradation mechanism. The BAC release in the uniaxial PLLA/BAC fibers mainly followed three stages. Firstly, as the BAC dropped from the surfaces of the PLLA through the interaction with PBS, there appeared some micropores serving as the channels of the fiber surfaces for the further release of BAC. Secondly, the BAC was released in the PLLA amorphous region, and the diffusion and release rates were slower than those in PBS because the BAC diffusion in PLLA mainly depended on the formed micropores. In other words, the BAC in the micropore surfaces was infiltrated by PBS, dissolved and diffused by the force of the concentration gradient. Thirdly, the BAC was released with the degradation and erosion of the PLLA of the crystalline region. These three stages happened successively and diffusion was the dominant dynamic force.

The BAC in the hydrophilic carrier PLL was released along with the PLL hydration expansion, surface erosion, and the diffusion of the BAC in the PLL. The release of the BAC in the PLLA/PLL fiber was the result of the interaction between the diffusion and corrosion of PLLA and PLL.

The uniaxial fibers belonged to the homogeneous mixing type drug delivery system in which the drug was uniformly dispersed into the carrier material and the drug release rate was dependent on the diffusion in the expanded polymer carrier. The coaxial drug-loaded fibers belonged to a storage reservoir type system and the drug was physically encapsulated in the polymer and the release of the drug mainly relied on the degradation and corrosion of the polymer carriers.

It can be illustrated by Fig. 4 and 6 that the drug release within 16 days in the coaxial fibers, such as the (PLLA/BAC)-(PLLA/PLL) fibers and (PLLA/PLL/BAC)-PLLA fibers, could be mainly divided into the following three periods (as in Fig. 4). In the first stage (the early 24 hours), the BAC in the generated fibers like A and C in Fig. 6 due to the split was exposed and peeled off from the external surface, then dissolved into the PBS, which caused faster release rates at the outset. The initial slight burst release emerged in both the (PLLA/BAC)-(PLLA/PLL) fibers and the (PLLA/PLL/BAC)-PLLA fibers, and the cumulative BAC release rate of the (PLLA/BAC)-(PLLA/PLL) was 40–45% while that of the (PLLA/PLL/BAC)-PLLA was 30–35%. The second stage was a transient stationary period from 24 h to 48 h when the drug in the fiber surface was almost completely released. In this situation, the drug release rates were slowing down because the core drug needed to diffuse through the shell materials and reached the surface of the fibers and was released with the degradation and erosion of the shell materials. The last stage from 48 h to 16 days showed a slow acceleration of the drug release rate, which could be attributed to the channels generated by the diffusion of drugs in the second phase.

The biexponential-biphase kinetics function is the most popular diffusion kinetics equation at present, and can be used to explain the release mechanism of the drug-loaded fibers in this experiment. A fitting process was conducted on the cumulative drug release rate along with the drug release period. The fitting curves are shown in Fig. 7 and the fitting results are shown in Table 3.

Fig. 7 Fitting curves of different drug-loaded fibers (a) PLLA/PLL/BAC; (b) PLLA/BAC; (c) (PLLA/BAC)-(PLLA/PLL); (d) (PLLA/PLL/BAC)-PLLA.

Table 3 The fitting results of different drug-loaded fibers

Drug-loaded fibers	Fitting results	R^2
PLLA/BAC		0.998
PLLA/PLL/BAC		0.998
(PLLA/BAC)-(PLLA/PLL)		0.997
(PLLA/PLL/BAC)-PLLA		0.995

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From the fitting curves, the initial burst releases of the uniaxial fibers were more obvious than those of the coaxial fibers because the shell materials of the coaxial fibers hindered the diffusion of the drug at the beginning. The controlled release of the coaxial fibers was more effective than that of the uniaxial fibers because of the impediment of the shell materials of the coaxial fibers. The drug release was proceeding with the degradation of the carriers. The major release of the drug in the uniaxial fibers resulted from the diffusion of the drug in the carrier, while the release of the drug in the coaxial fibers was the result of diffusion and corrosion at the same time.

The studies above have verified that fibers of different drug release patterns can be fabricated using uniaxial or coaxial electrospinning. The drug in the uniaxial fibers could be quickly released and the drug release pattern might reduce the effectiveness of drugs and cause side effects due to its burst release. However, this release is not always unsuitable, for example, this pattern of drug release is preferred in the case that large doses of drugs within a short time are needed in order to eliminate viruses and bacteria in antibiotic treatment. The drug release in the coaxial fibers is a kind of controlled release which is more suitable for the drug release systems of long-term and small-dose drugs, such as hormonal drugs and long-acting anticancer drugs. Additionally, the coaxial drug controlled release could reduce the harm in the human body in the process of taking drugs with toxic effects. For drug producers, different drug-loaded patterns can be chosen according to different therapeutic purposes.

Conclusions

In this study, BAC was encapsulated into PLLA and PLLA/PLL as a kind of controlled-release drug. The interaction between the drug and the carriers was mainly physical and most of the BAC was embedded in the electrospun fibers, as assessed using FT-IR, DSC and SEM. The uniaxial drug-loaded fibers showed a higher release rate than the coaxial drug-loaded fibers did, and the drug release rate of the uniaxial PLLA/PLL/BAC fiber was the fastest among the fibers. The drug release rates of these fibers with PLL were higher than those of the fibers without PLL due to the hydrophilicity of PLL. The fibers with different drug release patterns were achieved using the uniaxial and coaxial electrospinning processes. The drug in the uniaxial fibers could be quickly released while the drug in the coaxial fibers showed a kind of slow and controlled release. The drug release of these drug-loaded fibers conformed to the biexponential-biphase kinetics equation. The drug release mechanism of the uniaxial fibers was mainly diffusion while that of the coaxial fibers was the conjunct effect of drug diffusion and carrier corrosion.

Acknowledgements

This work was supported by the Northwestern Polytechnical University Fundamental Research Fund under Grant (JCY20130148).

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