Tannic Acid-Stabilized Self-Degrading Temperature-Sensitive Poly(2-n-propyl-2-oxazoline)/Gellan Gum Capsules for Lipase Delivery

Abstract

In recent years, stable hydrogen-bonded stimuli-responsive polymer capsules have been receiving great interest for the encapsulation and release of sensitive molecules such as lipase enzymes. Compartmental capsules having a liquid gel core stabilized with temperature-responsive hydrogen-bonded multilayers are advantageous over other conventional systems because of their ability to maintain hydrophilic lipase and other hydrophobic compounds in compatible protected molecular vehicle environments and prolong their native properties, e.g., in the body. In this work, we report a methodology to stabilize an aqueous liquid gellan gum (GG) core in a capsule using neutral and nontoxic building blocks, namely, poly­(2-n-propyl-2-oxazoline) (PnPrOx) and tannic acid (TA), to fabricate temperature-responsive capsules, comprising both lipase and hydrophobic oil droplets. The capsules were fabricated by adding GG droplets to a PnPrOx suspension at a temperature (T) higher than its cloud point temperature (T CP). Notably, the formed capsules were not stable in water without TA stabilization via hydrogen bonding. Scanning electron microscopy (SEM) investigations of the GG/building block interphase revealed that the collapsed PnPrOx globules that are present above the T CP stabilized the GG interphase as a Pickering emulsion, while undergoing a configurational transformation into its linear form by interacting with TA in the next step of capsule formation resulting in a smooth PnPrOx/TA capsule wall. The encapsulation efficiencies of the capsules for model fluorescent molecules were found to be 52, 54, and 24% for FITC-dextran, rhodamine, and Nile red, respectively. The stability experiments exhibited swelling and shell thinning at certain locations followed by complete rupture of the capsules at 37 °C, while the capsules were stable for several weeks at temperatures below the T CP of PnPrOx. The capsules were found to be stable in stimulated gastric fluid (SGF) for several hours at 37 °C while successfully releasing the encapsulated lipase and Nile red (model hydrophobic compound) in stimulated intestinal fluid (SIF). The released lipase was found to retain almost 100% of its activity. The reported capsules have high potential for use as carriers for encapsulation and release of a variety of payloads ranging from proteins and vitamin supplements to enzymes and probiotics through the oral route of administration.

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“…The spectrum of the control TA/P n PrOx nanocapsule showed the major characteristic peaks of TA and P n PrOx at 1530, 1200, 1632, 2973, and 1400 cm –1 , which can be assigned to carboxylate (−COO – ) asymmetric stretching vibrations, bending vibrations of C–O and C=C associated with phenolic hydroxyl groups of TA, CH 2 stretching vibrations, and CH 3 symmetrical deformation of P n PrOx, respectively. Further, a broad band appeared at 3424 cm –1 indicating the formation of hydrogen bonds between the phenol groups of TA and the amide groups of P n PrOx. , Similarly, the TA/P n PrOx/AuNRs spectrum showed two clearly visible additional peaks at 2873 and 2923 cm –1 , corresponding to C–H stretching vibrations of the methyl and methylene groups of CTAB, thus indicating the successful entrapment of AuNRs in the nanocapsules . The spectrum of TA/P n PrOx/AuNRs/FAQDs also showed the major characteristic peaks of FA at 1405, 1618, 1118, and 1336 cm –1 attribute to the carboxyl groups, asymmetric stretching and bending vibrations of C–N and C=N of the pterin ring. , The absorption peaks at 3250 and 1645 cm –1 are attributed to N–H stretching vibrations and C=O stretching vibrations of FA associated with FAQDs.…”

“…Further, a broad band appeared at 3424 cm −1 indicating the formation of hydrogen bonds between the phenol groups of TA and the amide groups of PnPrOx. 25,26 Similarly, the TA/PnPrOx/ AuNRs spectrum showed two clearly visible additional peaks at 2873 and 2923 cm −1 , corresponding to C−H stretching vibrations of the methyl and methylene groups of CTAB, thus indicating the successful entrapment of AuNRs in the nanocapsules. 43 The spectrum of TA/PnPrOx/AuNRs/ FAQDs also showed the major characteristic peaks of FA at 1405, 1618, 1118, and 1336 cm −1 attribute to the carboxyl groups, asymmetric stretching and bending vibrations of C−N and C=N of the pterin ring.…”

“…Our previous investigations demonstrated that the capsules undergo a configurational transformation from an extended hydrated form to a collapsed globular form at a physiological temperature of 37 °C. Subsequently, the pore formation followed by the rupture of capsules was observed as a function of time. ,, As a result, the total release has two components: (i) diffusion-induced release due to the concentration gradient across the intact shell, and (ii) release induced by the morphological transition of TA/P n PrOx shell from a pore-free smooth structure to a porous structure at 37 °C. To differentiate the release contribution from each one of them, two different sets of experiments were performed at both 37 °C (physiological temperature, above the T CP ) and 16 °C (below the T CP ) in the same conditions.…”

“…Furthermore, at a physiological temperature of 37 °C, PnPrOx undergoes a morphological transition from a hydrated coil to a dehydrated globular form, thereby providing the option to design a temperature-responsive system. 25 Our previous investigations have demonstrated the successful fabrication of PnPrOx/TA films and capsules reinforced by a combination of hydrophobic interactions and hydrogen bonding. The films remain stable over a pH range of 2 to 9, whereas their permeability was enhanced at higher temperatures by undergoing configurational reorganization of the capsule's shell associated with the lower critical solution temperature transition of PnPrOx.…”

“…In recent years, poly­(2-alkyl-2-oxazoline) (PAOx)-based hydrogen-bonded multilayer hollow capsules emerged as promising carriers for drug delivery applications because of the structural similarity of PAOx to peptides, antibiofouling characteristics, stimuli-responsiveness against pH and temperature, and biocompatibility. − Among the reported PAOx systems, poly­(2- n -propyl-2-oxazoline) (P n PrOx) is an interesting polymer with a cloud point temperature ( T CP ) of ∼25 °C and high stability in the pH range between 2 and 9. Furthermore, at a physiological temperature of 37 °C, P n PrOx undergoes a morphological transition from a hydrated coil to a dehydrated globular form, thereby providing the option to design a temperature-responsive system . Our previous investigations have demonstrated the successful fabrication of P n PrOx/TA films and capsules reinforced by a combination of hydrophobic interactions and hydrogen bonding.…”