pH sensitive amphiphilic conetworks based on end-group cross-linking of polydimethylsiloxane pentablock copolymer and polymethylhydrosiloxane

Abstract

A series of pH-responsive amphiphilic conetworks (APCNs) were synthesized through cross-linking of well-defined amphiphilic pentablock copolymers via atom transfer radical polymerization (ATRP). A new ditelechelic polydimethylsiloxane macroinitiator was synthesized to initiate the polymerization of N,N-dimethylaminoethyl methacrylate. The resulting triblock copolymers showed well-defined molecular weight with narrow polydisperisty, which were used as macroinitiator to incorporate allyl methacrylate to get the pentablock copolymers with allyl pendant groups. Then, pentablock copolymers were fully cross-linked with polyhydrosiloxanes through hydrosilylation. The so-prepared APCNs exhibited unique properties of microphase separation of hydrophilic (HI) and hydrophobic (HO) phases with small channel size, a variable swelling capacity in media with different pH and polarity, a good mechanical property (1.3 ± 0.2 MPa) and outstanding oxygen permeability (300 ± 120 barrers). The properties of APCNs depend on the ratio of HI–HO, which can be regulated via precise synthesis of the triblock copolymers. The APCNs showed well-controlled drug release to Rhodamine 6G upon varying the pH. Meanwhile, the controlled manner is also attributed to the well-defined molecular structure and tunable HI/HO composition of the APCNs.

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Introduction

As the rapidly emerging novel materials that consist of covalently interconnected hydrophilic and hydrophobic polymer chains,^1–4 amphiphilic conetworks (APCNs) have many unique properties, such as swelling dependence on solvent, microphase separation structure and biocompatibility, which make them promising for applications in a wide variety of areas.^5–15

The APCNs prepared from polydimethylsiloxane (PDMS)^16,17 have received great attention due to its own characteristics, i.e. excellent biocompatibility, high elasticity, heat resistance, low surface free energy, biological inertness as well as the highest oxygen permeability among all polymers, which shows a wide range of potential applications in intelligent polymer materials, soft contact lenses, biomedical materials, antifouling surfaces and biochemical sensors.^18,19 Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), one of the well-investigated hydrophilic polymers with thermo and pH sensitivity,^20–24 has potential applications in drug delivery and release,^25,26 gene carrier,^27,28 and antibacterial surface.^29,30 Patrickios' group^31–36 has prepared PDMAEMA-based APCNs with different architecture and studied their swelling property, degradation characteristics, storage and delivery of DNA. Therefore, an APCN consisting of PDMAEMA and PDMS segments is of great interest due to the distinguished characteristics of segment, its microphase separation, physiological inertness and biocompatible properties. However, there is no report to our knowledge about the synthesis of such a conetwork.

Most APCNs reported are synthesized by uncontrollable free radical polymerization,^37–39 which inevitably leads to bad conformation regularity, structure defect or even loss of performance. To minimize the defects, more recently APCNs have been prepared by cross-linking polymer chains of well-defined length using controlled methods, such as quasiliving carbocationic polymerization (QLCCP), group transfer polymerization (GTP), reversible addition fragmentation chain transfer (RAFT) polymerization and atom transfer polymerization (ATRP).^35,40–43 Among these methods, ATRP has shown outstanding capability to prepare hydrogels and APCNs with well-defined molecular structure and good mechanical properties,^42,44 and the use of macroinitiator has received much attention because it simplifies the synthesis step and has a high tolerance for functional groups and impurities.⁴⁵ In this study, polydimethylsiloxane-di-2-bromoisobutyrate (Br-PDMS-Br) initiates the ATRP of DMAEMA (Scheme 1), and the resulting well-defined PDMAEMA-b-PDMS-b-PDMAEMA triblock copolymers was used as the macroinitiator for the ATRP of allyl methacrylate due to the preservation of active alkyl halide chain end. The introduction of poly (allyl methacrylate) (PAMA) units in the resulting pentablock copolymers guarantees the full cross-linking of the resulting APCN since the allyl pendant groups act as crosslinking sites with polymethylhydrosiloxane. The good water swelling property as a function of pH, excellent mechanical properties and interesting drug release profile of prepared APCN suggest a promising excellent carrier for controlled release.

Scheme 1 Schematic diagram illustrating the preparation of pentablock copolymer via ATRP and crosslinking APCNs with PMHS.

Experimental part

Materials

N,N-Dimethylaminoethyl methacrylate (DMAEMA) and allyl methacrylate (AMA) were purchased from Energy Chemical Co. and purified by passing through a basic silica column to remove the inhibitor. Hydroxypropyl polydimethylsiloxane (PDMS, M_n = 4000 g mol⁻¹, PDI = 1.41), polymethylhydrosiloxane (PMHS, M_n = 6000 g mol⁻¹, PDI = 1.40) and Karstedt's catalyst (3% Pt(0) in xylene) were purchased from Gelest and were used as received. Copper(I) bromide was purchased from Shanghai Chemical Reagent Plant and was purified according to a standard procedure.⁴⁶ N,N,N′,N′,N′′-pentamethyldiethylenetriamine (PMDETA), anhydrous magnesium sulfate (MgSO₄), Rhodamine 6G and 2-bromoisobutyryl bromide were purchased from Aldrich and used as received.

Synthesis of macroinitiator Br-PDMS-Br

Hydroxypropyl polydimethylsiloxane (30 g, 7.5 mmol) and triethylamine (1.59 g, 15.8 mmol) were dissolved in 200 mL dry THF in a three-neck round bottomed flask. 2-bromoisobutyrate (3.45 g, 15.0 mmol) was added dropwise to the stirred solution at 0 °C for 1 h. The reaction was stopped after stirring at room temperature for 16 h, filtered to remove the triethylamine hydrobromide byproduct, and evaporated under vacuum. The resulting liquid was redissolved in hexane and washed with a saturated aqueous sodium hydrogen carbonate solution three times. The organic layer was dried by anhydrous magnesium sulfate. The final PDMS macroinitiator (Br-PDMS-Br) was obtained as a slightly yellow liquid with a yield of 95%. ¹H NMR (400 MHz, CDCl₃, Me₄Si, δ): 0.00 (m, 6H), 0.079 (s, 6H, Si(CH₃)₂), 0.87 (m, 2H, SiCH₂CH₂CH₂), 1.6 (m, 2H, SiCH₂CH₂CH₂), 4.33 (m, 2H, SiCH₂CH₂H₂), 1.96 (s, 6H, BrC(CH₃)₂).

Synthesis of PDMAEMA-b-PDMS-b-PDMAEMA triblock copolymers

A series of triblock copolymers were synthesized by ATRP. In a typical experiment, Br-PDMS-Br macroinitiator (1.00 g, 0.25 mmol), PMDETA (0.865 g, 0.5 mmol) and CuBr (0.072 g, 0.5 mmol) were added to a Schlenk flask (100 mL) equipped with a magnetic stirring bar and degassed three times. DMAEMA (7.85 g, 50 mmol) and isopropanol (15 mL) were then injected into the reaction flask. The flask was placed in a thermostated bath at 60 °C for 12 h. The mixture was then diluted with THF and passed through a basic alumina column to remove the copper residue and evaporated until dry. The crude product was redissolved in THF and precipitated in cold hexane twice, prior to being dried for 24 h in a vacuum oven. ¹H NMR (400 MHz, CDCgl₃, Me₄Si, δ): 0.00 (m, 6H), 0.079 (s, 6H, Si(CH₃)₂), 1.1–0.94 (3H, m, CH₂C(CH₃)CO), 1.9–2.0 (m, 2H, CH₂C(CH₃)CO), 2.35 (m, 6H, N(CH₃)₂), 2.75 (m, 2H, COCH₂CH₂N(CH₃)₂), 4.13 (m, 2H, COCH₂CH₂N(CH₃)₂).

Synthesis of PDMS-based pentablock copolymers

The pentablock copolymers were synthesized using a molar feed ratio [AMA (0.6 g)] : [CuBr] : [PMDETA] of 50 : 1 : 1 in 8 mL isopropanol at 60 °C involving 2 g triblock polymers for 18 h. The operations were done using the same procedures as described above. ¹H NMR (400 MHz, CDCgl₃, Me₄Si, δ): 0.00 (m, 6H), 0.079 (s, 6H, Si(CH₃)₂), 1.1–0.94 (3H, m, CH₂C(CH₃)CO), 1.9–2.0 (m, 2H, CH₂C(CH₃)CO), 2.35 (m, 6H, N(CH₃)₂), 2.75 (m, 2H, COCH₂CH₂N(CH₃)₂), 4.13 (m, 2H, COCH₂CH₂N(CH₃)₂), 4.46 (m, 2H, OCH₂CHCH₂), 5.30 (m, 1H, CH₂CHCH₂, allyl), 5.9 (m, 2H, CH₂CHCH₂, allyl).

Synthesis of amphiphilic conetworks

PAMA-b-PDMAEMA-b-PDMS-b-PDMAEMA-b-PAMA (1 g), PMHS (0.1 g) and Karstedt's catalyst (50 μL) was dissolved in 20 mL toluene and the mixture was stirred at room temperature for 12 h. Then the homogeneous solution was poured into a Teflon mold (3 × 3 cm) and placed in an oven at 60 °C for 24 h. After crosslinking, the formed film was extracted by THF, and dried in vacuo at room temperature.

Characterization techniques

Proton nuclear magnetic resonance spectroscopy

¹H NMR spectra was performed at room temperature on a Bruker Avance 400 instrument using CDCl₃ solutions with tetramethylsilane (TMS) as an internal standard.

Fourier transform infrared spectroscopy

FT-IR spectra were obtained with a Nicolet Instrument Nicolet 8700 spectrometer. The sample was dispersed in a KBr disk.

Gel permeation chromatography

GPC was performed on a BI-MwA Gel Permeation Chromatography (Waters, Milford, MA), equipped with a light scattering instrument (Brookhaven, Holtsville, NY) at room temperature, using THF as the eluent at a flow rate of 0.8 mL min⁻¹ with a polystyrene standard as the reference.

Determination of the sol fraction

The sol fraction was determined by extracting a freshly synthesized APCN with THF for 72 h. The sol fraction was calculated as the ratio of the mass of the extractable mixture divided by the mass of virgin conetwork.
where m_q is the dry mass of the extracted samples and m₀ is the dry mass of the virgin sample.

Measurement of the swelling ratio

Swelling experiments were carried out at room temperature by immersing a pre-weighed sample in an excess of distilled water, THF, hexane and aqueous solutions of different pHs, respectively. The extent of swelling was determined by periodically taking the samples from the solvent, removing the solvent adsorbed to the surfaces by blotting with tissue paper, and the equilibrium swelling ratio (S_w) was recorded when the weight of the swollen samples remained unchanged for 48 h. The swelling ratio was calculated as following equation:
where m_t is the mass of the swollen samples and m₀ is the mass of the dry sample.

Measurement of the degree of ionization

The degree of ionization of APCN was calculated as the ratio of added HCl equivalents divided by the number of DMAEMA unit equivalents (calculated from the conetwork dry mass and conetwork composition) present in the sample. The acid titration curves were obtained by plotting the calculated degrees of ionization against the measured solution pH.

Tensile strength and elongation at break

The tensile strength and elongation at a break of APCN were measured by Universal Testing Machine (KEXIN, WDW3020, China) in water-swollen state. The samples were formed into rectangles (6 × 2 cm) and the tensile speed was set at 10 mm min⁻¹. Each sample was measured three times, respectively, and the average value was obtained. The error was less than 5%.

Oxygen permeability

Apparent oxygen permeability of APCN was determined at 35 °C. The instrument used together with specifications and the operational principle were described in detail.⁴⁷ To obtain comparable results with different compositions, the membranes were of the same dimensions (4 cm × 4 cm × 0.2 mm) and measurements were carried out under the same conditions.

Atomic force microscopy

AFM images were recorded with a Veeco Dimension Icon Scanning Probe Microscope (Veeco Instruments) in tapping mode using silicon cantilevers from Mikromasch USA with resonance frequencies of about 160 kHz, spring constants of 10.0 N m⁻¹.

Loading and in vitro release of drug

The dried APCNs were immersed in 30 mL aqueous solution of Rhodamine 6G (20 mg mL⁻¹) at room temperature for 72 h. Then the samples swollen to equilibrium were taken out and washed with water to remove the drug residues on the surface. The APCNs loaded with drugs were dried under vacuum for 2 days. These samples were used for drug release experiments without any further treatment. The amounts of drug loading in the conetworks were estimated in an indirect way. Rhodamine 6G in the conetworks exhibited the same molar absorption coefficient (530 nm) in the UV spectra as the free drugs. The amount of drug loading and encapsulation efficiency were calculated using the following equation.

where C₀ and C_t are concentrations at different time (μg mL⁻¹), V is the volume of solution (mL), M is the weight of the conetwork (g) and m is the weight of drug in feed (μg).

In vitro release studies were performed in water. The samples loaded with the drug were immersed in 50 mL water at pH 7.4 and 5.2, respectively. 3 mL of the solution was withdrawn from the release medium at intervals and replaced with 3 mL fresh water. The cumulative percentage of drug release was calculated as the average of three determinations and the standard deviations did not exceed 3%.

Results and discussion

Scheme 1 illustrates the synthetic strategy for a novel family of APCNs. The first step is the synthesis of PDMS macroinitiator by coupling commercially available hydroxypropyl polydimethylsiloxane with 2-bromoisobutyryl bromide. As far as PDMS-based copolymer is concerned there are few reports of controlled synthesis of amphiphilic block copolymers. Meier et al. reported the synthesis of PDMS-based amphiphilic block copolymers via ATRP using PDMS-based macroinitiator.⁴⁸ Bas and co-workers reported the controlled synthesis of PDMS-based triblock copolymers.⁴⁹ Here, a triblock copolymer PDMAEMA-b-PDMS-b-PDMAEMA was synthesized via ATRP of DMAEMA using Br-PDMS-Br macroinitiators and CuBr/PMDETA catalyst system. The synthesis of pentablock copolymer with allyl groups on ends is the key for preparation of well-defined amphiphilic conetworks, therefore, the incorporation of AMA segment through ATRP using PDMAEMA-b-PDMS-b-PDMAEMA macroinitiator produced pentablock copolymer with well-defined molecular weight and narrow molecular weight distribution. AMA has a conjugated methacrylic and an unconjugated allylic group. The former group has higher reactivity to form copolymers with allyl pendant groups. The present research was concerned with the synthesis of APCNs by combining amphiphilic pentablock copolymers with the polymethylhydrosiloxane (PMHS) through hydrosilylation. There exists an average of 100 Si–H pendant bonds per PMHS chain available for hydrosilylation, which means that the PDMAEMA-b-PDMS-b-PDMAEMA acts as cross-linker for the PMHS chains. Therefore, the important difference between the conetworks obtained by free radical copolymerization of functional macromonomers and the present work is the specific average chain length and relatively narrow molecular weight distribution of the PAMA-b-PDMAEMA-b-PDMS-b-PDMAEMA-b-PAMA chains in comparison with the broad distribution of the cross-linked chains in the conetworks prepared by conventional free radical copolymerization of telechelic macromonomers with low molecular weight monomers.

Polymer synthesis

Well-defined PDMAEMA-b-PDMS-b-PDMAEMA triblock copolymers and PAMA-b-PDMAEMA-b-PDMS-b-PDMEMA-b-PAMA pentablock copolymers are summarized in Table 1. The triblock copolymers with different block lengths of PDMAEMA were synthesized by varying the reaction time. As the reaction time was increased from 12 to 24 h, M_n of the copolymer increased from 13 400 to 31 000. The PDI of the triblock copolymers increased only slightly from 1.18 to 1.24 and their GPC traces were all symmetrical monomodal (Fig. 1), which indicates that no side-reactions occurred during the polymerizations. The relatively wide PDI of PDMS macroinitiator, i.e.1.41, did not influence the low PDI of the resulting copolymer, which narrowed down with increasing PDMAEMA chain length, indicating that the polymerization of DMAEMA proceeded in a controlled manner. As ATRP process occurs at a rate balance between activation (K_act) and deactivation (K_deact), the rate of reaction is not as high as radical polymerization reaction. When the conversion reaches a high level, the rate of propagation slows down considerably, the rate of any side reaction increases, leading to an increasing PDI of the final polymer. Pentablock copolymers were synthesized by ATRP using triblock copolymers as the macroinitiators. However, the chain length of triblock copolymers influence the activity of alkyl halide chain ends, the larger the molecular weight of the triblock copolymer is, and the lower the activity of alkyl halide becomes. Therefore, the number of AMA repeat units in the pentablock copolymers decreases with increasing PDMAEMA chain length, i.e. 40, 34 and 26, respectively. The PDI of the pentablock copolymers remain almost the same as the triblock copolymers, indicating the polymerization is controllable.

Table 1 Characterization of the PDMAEMA-b-PDMS-b-PDMEMA triblock copolymers and PAMA-b-PDMAEMA-b-PDMS-b-PDMEMA-b-PAMA pentablock copolymers synthesized by ATRP

Polymer structure^a	Reaction time (h)	Mn,cal^b (kDa)	Mn,NMR^c (kDa)	Mn,GPC^d (kDa)	PDI
a D, DMAEMA; P, PDMS; A, AMA. The subscript means the number of the unit, calculated from NMR.b Calculated from ^1H NMR based on PDMS unit (6H at 0.09 ppm), DMAEMA unit (2H at 4.1 ppm), AMA unit (2H at 4.5 ppm).c Determined by GPC measurement using polystyrene standards.d Theoretical Mn = [monomer]/[initiator] × (monomer conversion) × (monomer molecular weight) + (initiator molecular weight).
D30-b-P54-b-D30	12	14.0	13.4	17.8	1.20
D61-b-P54-b-D61	18	18.8	23.2	23.4	1.18
D86-b-P54-b-D86	24	30.7	31.0	35.8	1.24
A20-b-D30-b-P54-b-D30-b-A20	18	17.2	18.5	20.8	1.26
A17-b-D61-b-P54-b-D61-b-A17	18	25.3	27.5	31.5	1.21
A13-b-D86-b-P54-b-D86-b-A13	18	32.8	34.3	37.9	1.33

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Fig. 1 GPC traces of D_x-b-P₅₄-b-D_x triblock copolymers and A₁₃-b-D₇₆-b-P₅₄-b-D₇₆-b-A₁₃ pentablock copolymer. D, P and A are further abbreviations for DMAEMA, PDMS and AMA, respectively. The subscript means the number of repeat units.

The compositions of the copolymers were first determined by ¹H NMR. Fig. 2(a) shows the ¹H NMR spectrum of the Br-PDMS-Br macroinitiator. The chemical shift at 1.92 ppm was assigned to the protons (d, BrC(CH₃)₂) of the 2-bromoisobutyryl groups. The chemical shift at 4.12 ppm was attributed to the protons adjacent to the oxygen moiety (e, OCH₂). From the area ratio of peak d and peak e, the extent of halogenation in the Br-PDMS-Br macroinitiator was determined to be 90.8%. Fig. 2(b) and (c) show the ¹H NMR spectra of PDMAEMA₃₀-b-PDMS₅₄-b-PDMAEMA₃₀ and PAMA₂₀-b-PDMAEMA₃₀-b-PDMS₅₄-b-PDMAEMA₃₀-b-PAMA₂₀, respectively. The signals at 2.35, 2.63 and 4.12 ppm were mainly assigned to the methylene (d, NCH₂) and methyl (e, N(CH₃)₂) and methylene (f, COOCH₂) protons of the DMAEMA units. The chemical shifts at 4.50, 5.32 and 5.89 ppm correspond to the protons in allyl group of the AMA units, indicating the successful incorporation of AMA. To further confirm the structure of the copolymer, FT-IR measurement was utilized to characterize the block copolymer. Fig. 3 shows the FT-IR spectra of D₃₀-b-P₅₄-b-D₃₀ and A₂₀-b-D₃₀-b-P₅₄-b-D₃₀-b-A₂₀, respectively, where the three strong tertiary amide absorption bands at about 2825 cm⁻¹, 2764 cm⁻¹, 1266 cm⁻¹ were associated with the DMAEMA block. The intensities of the peak at about 1736 cm⁻¹ increased significantly with the incorporation of AMA. The characteristic band of the AMA component at about 1640 cm⁻¹ was observed in the FT-IR spectra of the A₂₀-b-D₃₀-b-P₅₄-b-D₃₀-b-A₂₀.

Fig. 2 ¹H NMR spectra of (a) Br-PDMS-Br; (b) D₆₁-b-P₅₄-b-D₆₁; (c) A₁₇-b-D₆₁-b-P₅₄-b-D₆₁-b-A₁₇ in CCl₃D.

Fig. 3 The FT-IR spectra of (a) D₆₁-b-P₅₄-b-D₆₁ and (b) A₁₇-b-D₆₁-b-P₅₄-b-D₆₁-b-A₁₇.

Characterization of the APCNS

Sol fraction of the conetworks. Table 2 shows the compositions of APCNs and the sol fraction extracted from each conetwork. In all cases the sol fraction was relatively low, with the lowest value being as low as 4.5% and the highest 8.5%, indicating essentially complete crosslinking and control over the conetwork structure.

Table 2 Fabrication composition of conetworks and corresponding sol fraction percentage and thickness

Sample	Block used (g)	PMHS crosslinker (g)	Total DMAEMA (w %)	Sol fraction (w/w%)	Thickness (mm)
APCN-1	0.56	0.30	33.2	4.5	0.20 ± 0.02
APCN-2	0.80	0.30	50.7	6.3	0.19 ± 0.03
APCN-3	0.97	0.30	60.1	8.5	0.20 ± 0.04

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Characterization of the degree of swelling of the APCNs. One of the most attractive characteristics of APCN is its property in different solvents due to the existence of both HO and HI phases in conetworks. Fig. 4 shows the S_w of APCN-3 in THF, neutral water and hexane. THF is a good solvent for both PDMS and DMAEMA, which APCN can fully swell. In contrast to THF, pure water is a good solvent for DMAEMA but poor for PDMS and AMA units, leading to lower S_w in neutral water than in THF. Fig. 4(c) shows the swelling ratios of APCNs in hexane, which is a good solvent for PDMS and AMA but poor for DMAEMA. The S_w value of APCN-3 in hexane was smaller than that in neutral water as APCN-3 has more hydrophilic phase than hydrophobic phase.

Fig. 4 Degrees of swelling of APCN-3 in (a) THF, (b) H₂O and (c) hexane.

Fig. 5 shows both the degree of swelling and the calculated degree of ionization of APCN-3 against the solution pH. The S_w increased as the pH decreased. Because the DMAEMA units become protonated at low pH, which resulted in the establishment of an osmotic pressure within the conetwork from the counter ions to the charged DMAEMA units and creation of electrostatic repulsions between the polymer chains.³¹ The degrees of swelling and the calculated degrees of ionization of APCN-1 and APCN-2 have the same changing trend as the APCN-3. In addition, the APCNs do not start to swell at the same pH, which was influenced by their composition.

Fig. 5 Aqueous degree of swelling and degree of ionization of the APCN-3 as a function of the solution pH.

Effective pK_as of the conetworks. The effective pK_a values of the DMAEMA units in the conetworks were taken from Fig. 5 and presented in Table 3. The pK_a of PDMAEMA was approximately 8, while the effective pK_a values of the DMAEMA units in all conetworks were significantly lower, at a range from 5.2 to 5.8, which was attributed to the polyelectrolyte effect, Donnan equilibrium and the reduction of the conetwork dielectric constant induced by the presence of the hydrophobic units.³¹ This phenomenon showed similar tendency with other conetwork studies.^31,36

Table 3 pK_as of the DMAEMA monomer repeating units in the end-linked conetworks

Sample	pKa
APCN-1	5.2
APCN-2	5.7
APCN-3	5.8

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Mechanical properties of the conetworks. As shown in Fig. 6, the tensile strengths of all the APCNs exceeded 1 MPa at water-swollen state, which are 3 times to other conetwork that contained DMAEMA and ε-caprolactone (CL) through ATRP reported in the literature, i.e., 0.37 MPa.⁵⁰ This phenomenon is mainly contributed by the existence of PDMS phase, which reinforced the hydrophilic PDMAEMA phase. Moreover, ATRP avoids the formation of inhomogeneity throughout the conetwork structure as usually encountered with an uncontrolled polymerization. Fig. 6 shows a decrease in tensile strength and an increase in elongation ratio with increasing PDMAEMA block length into APCN.

Fig. 6 The mechanical properties of all APCNs.

Oxygen permeability. High oxygen permeability is a key requirement for a biological device and we focus on this requirement when constructing the APCN. Fig. 7 shows the apparent oxygen permeability of water-swollen PDMAEMA_x-b-PDMS₅₄-b-PDMEMA_x/PMHS membranes as a function of PDMAEMA segment chain length. The data were collected by using 0.2 mm thick membranes and the boundary layer effect was not taken into account. Therefore, the true permeability was slightly higher than those test values.

Fig. 7 Oxygen permeability of APCNs as a function of PDMAEMA content (1 barrer = 10⁻¹¹ (cm² s⁻¹)(mL of O₂ (STP))/(mL mmHg)).

As shown in Fig. 7, oxygen permeability decreased from 420 to 181 barrers by increasing the PDMAEMA content from 33 to 61%. This trend is not surprising in view of the high gas permeability of PDMS and low oxygen permeability of hydrogels. It is noteworthy that the oxygen permeability of the present APCN, even those containing relatively large amounts of PDMAEMA, were similar to the best commercial extended-wear soft contact lenses, i.e. 195 ± 4 barrers.⁵¹ Therefore, the resulting APCNs exhibited very high oxygen permeability.

Atomic force microscopy. Atomic force microscopy (AFM) was used to visually investigate the morphology of the APCNs. Fig. 8 displays the AFM images (phase mode) of the surface of the conetworks, which depicts the nanoscale phase separation. The soft PDMS appears darker. Brighter structures are related to the brittle PDMAEMA. It is obvious that APCN-3 has larger brighter domain than the APCN-1, which is in agreement with the fact that APCN-3 has a higher HI content.

Fig. 8 AFM phase mode images on the surface of APCN-1 and APCN-3. In the tapping mode, PDMS shows dark and DMAEMA show light.

In vitro drug release studies. The DMAEMA-based hydrogels and APCNs have been widely explored as a drug carriers.^25,26,52 Herein, a highly water-soluble dye, Rhodamine 6G was used for loading and in vitro release from the prepared APCNs. Table 4 shows the amount of drug loading and encapsulation efficiency of the APCNs. The results show a similar drug loading levels of APCNs, indicating that the drug loading levels were dominated by the swelling ratio (S_w) of the APCNs rather than the hydrophilic (HI)/hydrophobic (HO) composition. The larger S_w of APCNs allows more Rhodamine 6G solution encapsulation, and thus a higher drug loading levels.

Table 4 Drug loading levels and encapsulation efficiency of APCNs

Sample	Weight of samples (g)	Drug loading (%)	Encapsulation efficiency (%)
APCN-1	0.33	2.2	1.2
APCN-2	0.55	5.3	4.8
APCN-3	0.54	7.1	6.4

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Fig. 9 presents the dissolution profile of pure Rhodamine 6G with a concentration of 0.2 g L⁻¹ and Rhodamine 6G in vitro release profiles from conetworks with different pHs. It can be clearly seen that the pure drug was completely released in water in 10 minutes, which accounts for the dissolution procedure of the drugs. But, all three conetworks were able to control the Rhodamine 6G release. APCN-3 exhibited a relatively faster drug release rate than APCN-1 and APCN-2 in water (pH = 7.4). Rhodamine 6G release was facilitated by the swelling behavior of conetworks with the diffusion as the driving force. APCN-3 has a high HI content, high S_w in water, which presents a fast drug release profile. And APCN-3 has less cross-linking point than APCN-1 and APCN-2, which also increased the drug release efficiency.

Fig. 9 Release kinetics of Rhodamine 6G from loaded APCNs.

APCN-3 was chosen for a pH-triggered release study. Fig. 9 shows the pH-sensitive drug release behavior of APCN-3 in pH 7.4 and pH 5.2 respectively, where APCN-3 in acid buffer (pH = 5.2) had a faster drug release profile, which was 15 percent more than in the neutral buffer (pH = 7.4). At low pH, the DMAEMA units became protonated, leading to an increase in hydrophilicity of polymer chains, which facilitated the drug escape from conetworks. Overall, the result showed that these conetworks respond to pH stimuli to control drug release.

Conclusions

Conclusively, we have described the synthesis of PDMAEMA-involved amphiphilic conetworks through cross-linking of amphiphilic pentablock copolymers via ATRP with well-defined molecular weight and narrow polydispersity. The APCNs exhibited unique pH-responsive swelling behavior, excellent mechanical properties, outstanding oxygen permeability and phase separation, which can be regulated via precise control of molecular structure and tunable HI/HO composition. The APCNs are suitable for controlled release of Rhodamine 6G, where the release rate can be regulated by varying the HI composition, cross-linking density and the pH of media. The ability of these APCNs to adsorb and desorb solutes in a controlled manner upon triggering the pH in aqueous media, may allow for their potential application as a carrier for controlled release.

Acknowledgements

This work was financially supported by National Science Foundation (NSF51103019, NSF21174027) and National High technology Research and Development Projects (863, 2012AA03A605). Program for New Centre Excellent Talents in University (12X10623).

Notes and references

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