HPMC/PVP K90 Dissolving Microneedles Fabricated from 3D-Printed Master Molds: Impact on Microneedle Morphology, Mechanical Strength, and Topical Dissolving Property.

Three-dimensional (3D) printing can be used to fabricate custom microneedle (MN) patches instead of the conventional method. In this work, 3D-printed MN patches were utilized to fabricate a MN mold, and the mold was used to prepare dissolving MNs for topical lidocaine HCl (L) delivery through the skin. Topical creams usually take 1-2 h to induce an anesthetic effect, so the delivery of lidocaine HCl from dissolving MNs can allow for a therapeutic effect to be reached faster than with a topical cream. The dissolving-MN-patch-incorporated lidocaine HCl was constructed from hydroxypropyl methylcellulose (HPMC; H) and polyvinyl pyrrolidone (PVP K90; P) using centrifugation. Additionally, the morphology, mechanical property, skin insertion, dissolving behavior, drug-loading content, drug release of MNs and the chemical interactions among the compositions were also examined. H51P2-L, H501P2-L, and H901P2-L showed an acceptable needle appearance without bent tips or a broken structure, and they had a low % height change (<10%), including a high blue-dot percentage on the skin (>80%). These three formulations exhibited a drug-loading content approaching 100%. Importantly, the composition-dependent dissolving abilities of MNs were revealed. Containing the lowest amount of HPMC in its formulation, H901P2-L showed the fastest dissolving ability, which was related to the high amount of lidocaine HCl released through the skin. Moreover, the results of an FTIR analysis showed no chemical interactions among the two polymers and lidocaine HCl. As a result, HPMC/PVP K90 dissolving microneedles can be used to deliver lidocaine HCl through the skin, resulting in a faster onset of anesthetic action.

Low cytotoxicity, antibacterial property, and curcumin delivery performance of toughness-enhanced electrospun composite membranes based on poly(lactic acid) and MAX phase (Ti3AlC2).

MXenes, synthesized from their precursor MAX phases, have been extensively researched as additives to enhance the drug delivery performance of polymer matrices, whereas there is a limited number of previous reports on the use of MAX phases themselves for such applications. The use of MAX phases can exclude the complicated synthesis procedure and lessen resultant production and environmental costs required to convert MAX phases to MXenes. Herein, electrospun membranes of poly(lactic acid) (PLA) and a MAX phase (Ti3AlC2) have been fabricated for curcumin delivery. The composite membrane exhibits significantly higher toughness (8.82 MJ m-3) than the plasticized PLA membrane (0.63 MJ m-3) with low cytotoxicity, supporting proliferation of mouse fibroblast L929 cells. The curcumin-loaded composite membrane exhibits high water vapor transmission (∼7350 g m-2 day-1), porosity (∼85 %), water wettability, and antibacterial properties against E. coli and S. aureus. Seven-day curcumin release is enhanced from 45 % (PLA) to 67 % (composite) due to curcumin diffusion from the polymer fibers and MAX phase surface that contributes to overall increased curcumin adsorption and release sites. This work demonstrates the potential of the MAX phase to enhance both properties and curcumin delivery, promising for other eco-friendly systems for sustainable drug delivery applications.

Surface-Modified Carboxylated Cellulose Nanofiber Hydrogels for Prolonged Release of Polyhexamethylene Biguanide Hydrochloride (PHMB) for Antimicrobial Applications.

The surface modification of cellulose nanofibers (CNFs) using a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)/sodium bromide (NaBr)/sodium hypochlorite (NaClO) system was successful in improving their hydrophilicity. Following that, we fabricated hydrogels containing carboxylated cellulose nanofibers (c-CNFs) and loaded them with polyhexamethylene biguanide (PHMB) using a physical crosslinking method, aiming for efficient antimicrobial uses. The morphological and physicochemical properties of all hydrogel formulations were characterized, and the results revealed that the 7% c-CNFs-2 h loaded with PHMB formulation exhibited desirable characteristics such as regular shape, high porosity, good mechanical properties, suitable gel content, and a good maximum swelling degree. The successful integration of PHMB into the c-CNF matrix was confirmed by FTIR analysis. Furthermore, the 7% c-CNFs-2 h loaded with the PHMB formulation demonstrated PHMB contents exceeding 80% and exhibited a prolonged drug release pattern for up to 3 days. Moreover, this formulation displayed antibacterial activity against S. aureus and P. aeruginosa. In conclusion, the novel approach of c-CNF hydrogels loaded with PHMB through physical crosslinking shows promise as a potential system for prolonged drug release in topical drug delivery while also exhibiting excellent antibacterial activity.

Antimicrobial thermoplastic starch reactive blend with chlorhexidine gluconate and epoxy resin.

An antimicrobial thermoplastic starch (TPS) was developed by melt-mixing TPS with chlorhexidine gluconate (CHG) and epoxy resin (Er). The tensile strength and hardness of the TPSCh blend increased with the addition of Er (TPSCh/Er), especially at 5 wt% Er (TPSCh/Er5) (19.5 MPa and 95 %, respectively). The water contact angle of TPSCh/Er was higher than those of TPS and TPSCh because of the improved interfacial tension. Fourier transform infrared and nuclear magnetic resonance analyses confirmed the reaction between the epoxy groups of Er, hydroxyl groups of starch, and amino groups of CHG. TPSCh/Er5 exhibited a significantly lower CHG release than TPSCh owing to the rearrangement of TPSCh chains via Er crosslinking. TPSCh/Er0.5 and TPSCh/Er1 showed inhibition zones against both tested bacteria (Staphylococcus aureus and Bacillus cereus), whereas TPSCh/Er2.5, TPSCh/Er5, and TPSCh/Er10 showed inhibition zones only against S. aureus. Moreover, TPSCh and TPSCh/Er0.5-2.5 exhibited inhibition zones with Saccharomyces cerevisiae.

Fabrication and Evaluation of Water Hyacinth Cellulose-Composited Hydrogel Containing Quercetin for Topical Antibacterial Applications.

Water hyacinth is an aquatic weed species that grows rapidly. In particular, it causes negative impacts on the aquatic environment and ecological system. However, water hyacinth is rich in cellulose, which is a biodegradable material. This study isolated cellulose from the water hyacinth petiole. It was then used to fabricate composite hydrogels made with water hyacinth cellulose (C), alginate (A), and pectin (P) at different mass ratios. The selected water hyacinth cellulose-based hydrogel was incorporated with quercetin, and its properties were evaluated. The FTIR and XRD of extracted water hyacinth cellulose indicated specific characteristics of cellulose. The hydrogel which consisted of the water hyacinth cellulose alginate characterized pectin: pectin had a mass ratio of 2.5:0.5:0.5 (C2.5A0.5P0.5), showed good puncture strength (2.16 ± 0.14 N/mm2), the highest swelling index (173.28 ± 4.94%), and gel content (39.35 ± 0.53%). The FTIR showed an interaction between water hyacinth cellulose and quercetin with hydrogen bonding. The C2.5A0.5P0.5 hydrogel containing quercetin possessed 92.07 ± 5.77% of quercetin-loaded efficiency. It also exhibited good antibacterial activity against S. aureus and P. aeruginosa due to hydrogel properties, and no toxicity to human cells. This study indicated that water hyacinth cellulose-composited hydrogel is suitable for topical antibacterial applications.

Dual Crosslinked Ion-Based Bacterial Cellulose Composite Hydrogel Containing Polyhexamethylene Biguanide.

Composite bacterial cellulose (BC) based hydrogel with alginate (A) or pectin (P) or alginate and pectin was fabricated via a physical crosslinking technique using calcium chloride (CaCl2) solution and incorporated with polyhexamethylene biguanide (PHMB) as an effective antimicrobial drug by immersion method. After that, the physicochemical properties of all hydrogel formulations were characterized. The result showed that the formulations with PHMB performed better physicochemical properties than the hydrogel without PHMB. Fourier transform infrared spectroscopy (FT-IR) showed the interaction between PHMB and the carboxylic group of alginate and pectin. BC/A-PHMB hydrogel performed suitable mechanical strength, fluid uptake ability, water retention property, drug content, high integrity value, and maximum swelling degree. Moreover, in vitro cell viability of BC/A-PHMB hydrogel revealed high biocompatibility with human keratinocyte cell line (HaCaT) and demonstrated prolong released of PHMB in Tris-HCl buffer pH 7.4, while rapid release in phosphate buffer saline pH 7.4. BC/A-PHMB hydrogel demonstrated good anti-bacterial activity against S. aureus and P. aeruginosa. In conclusion, BC/A-PHMB hydrogel could be a potential dual crosslinked ion-based hydrogel for wound dressing with anti-bacterial activity.

Development of Carboxymethyl Chitosan Nanoparticles Prepared by Ultrasound-Assisted Technique for a Clindamycin HCl Carrier.

Polymeric nanoparticles are one method to modify the drug release of small hydrophilic molecules. In this study, clindamycin HCl was used as a model drug loaded in carboxymethyl chitosan nanoparticles cross-linked with Ca2+ ions (CMCS-Ca2+). The ultrasonication with experimental design was used to produce CMCS-Ca2+ nanoparticles loading clindamycin HCl. The model showed that the size of nanoparticles decreased when amplitude and time increased. The nanoparticle size of 318.40 ± 7.56 nm, decreased significantly from 543.63 ± 55.07 nm (p < 0.05), was obtained from 75% of amplitude and 180 s of time, which was one of the optimal conditions. The clindamycin loading content in this condition was 34.68 ± 2.54%. The drug content in nanoparticles showed an inverse relationship with the size of the nanoparticles. The sodium carboxymethylcellulose film loading clindamycin HCl nanoparticles exhibited extended release with 69.88 ± 2.03% drug release at 60 min and a gradual increase to 94.99 ± 4.70% at 24 h, and demonstrated good antibacterial activity against S. aureus and C. acne with 40.72 ± 1.23 and 48.70 ± 1.99 mm of the zone of inhibition at 24 h, respectively. Thus, CMCS-Ca2+ nanoparticles produced by the ultrasound-assisted technique could be a potential delivery system to modify the drug release of small hydrophilic antibiotics.

Composite Nanocellulose Fibers-Based Hydrogels Loading Clindamycin HCl with Ca2+ and Citric Acid as Crosslinking Agents for Pharmaceutical Applications.

Biocomposite hydrogels based on nanocellulose fibers (CNFs), low methoxy pectin (LMP), and sodium alginate (SA) were fabricated via the chemical crosslinking technique. The selected CNFs-based hydrogels were loaded with clindamycin hydrochloride (CM), an effective antibiotic as a model drug. The properties of the selected CNFs-based hydrogels loaded CM were characterized. The results showed that CNFs-based hydrogels composed of CNFs/LMP/SA at 1:1:1 and 2:0.5:0.5 mass ratios exhibited high drug content, suitable gel content, and high maximum swelling degree. In vitro assessment of cell viability revealed that the CM-incorporated composite CNFs-based hydrogels using calcium ion and citric acid as crosslinking agents exhibited high cytocompatibility with human keratinocytes cells. In vitro drug release experiment showed the prolonged release of CM and the hydrogel which has a greater CNFs portion (C2P0.5A0.5/Ca + Ci/CM) demonstrated lower drug release than the hydrogel having a lesser CNFs portion (C1P1A1/Ca + Ci/CM). The proportion of hydrophilic materials which were low methoxy pectin and sodium alginate in the matrix system influences drug release. In conclusion, biocomposite CNFs-based hydrogels composed of CNFs/LMP/SA at 1:1:1 and 2:0.5:0.5 mass ratios, loading CM with calcium ion and citric acid as crosslinking agents were successfully developed for the first time, suggesting their potential for pharmaceutical applications, such as a drug delivery system for healing infected wounds.

Extraction of Tropical Fruit Peels and Development of HPMC Film Containing the Extracts as an Active Antibacterial Packaging Material.

In recent years, instead of the use of chemical substances, alternative substances, especially plant extracts, have been characterized for an active packaging of antibacterial elements. In this study, the peels of mangosteen (Garcinia mangostana), rambutan (Nephelium lappaceum), and mango (Mangifera indica) were extracted to obtain bioactive compound by microwave-assisted extraction (MAE) and maceration with water, ethanol 95% and water-ethanol (40:60%). All extracts contained phenolics and flavonoids. However, mangosteen peel extracted by MAE and maceration with water/ethanol (MT-MAE-W/E and MT-Ma-W/E, respectively) contained higher phenolic and flavonoid contents, and exhibited greater antibacterial activity against Staphylococcus aureus and Escherichia coli. Thus, both extracts were analyzed by liquid chromatograph-mass spectrometer (LC-MS) analysis, α-mangostin conferring antibacterial property was found in both extracts. The MT-MAE-W/E and MT-Ma-W/E films exhibited 30.22 ± 2.14 and 30.60 ± 2.83 mm of growth inhibition zones against S. aureus and 26.50 ± 1.60 and 26.93 ± 3.92 mm of growth inhibition zones against E. coli. These clear zones were wider than its crude extract approximately 3 times, possibly because the film formulation enhanced antibacterial activity with sustained release of active compound. Thus, the mangosteen extracts have potential to be used as an antibacterial compound in active packaging.

Preparation of Clindamycin Hydrochloride Loaded De-Esterified Low-Methoxyl Mango Peel Pectin Film Used as a Topical Drug Delivery System.

In this study, we aimed to develop a low-mexthoxyl pectin (LMP) from mango peel pectin through a de-esterification method for use as a film forming agent. The prepared de-esterified pectin (DP) was compared to commercial LMP (cLMP) which possessed a 29% degree of esterification (DE). Mango peel pectin was extracted from ripe Nam Dokmai mango peel using the microwave-assisted extraction method. Pectin derived from the mango peel was classified as a high mexthoxyl pectin (79% DE) with 75% of galacturonic acid (GalA) content. A de-esterification experiment was designed by central composite design to plot the surface response curve. Our prepared DP was classified as LMP (DE 29.40%) with 69% GalA. In addition, the Fourier-transform infrared spectrophotometer (FTIR) spectra of the DP were similar to cLMP and the pectin backbone was not changed by the de-esterification process. Strikingly, the cLMP and DP films showed non-significant differences between their physical properties (p > 0.05) with respect to the puncture strength (13.72 N/mm2 and 11.13 N/mm2 for the cLMP and DP films, respectively), percent elongation (2.75% and 2.52% for the cLMP and DP films, respectively), and Young's modulus (67.69 N/mm2 and 61.79 N/mm2 for the cLMP and DP films, respectively). The de-esterified pectin containing clindamycin HCl (DPC) and low-methoxyl pectin containing clindamycin HCl (cLMPC) films demonstrated 93.47% and 98.79% of drug loading content. The mechanical properties of the cLMPC and DPC films were improved possibly due to their crystal structures and a plasticizing effect of clindamycin HCl loaded into the films. The DPC film exhibited a drug release profile similar to that of the cLMPC film. Our anti-bacterial test of the films found that the cLMPC film showed 41.11 and 76.30 mm inhibitory clear zones against Staphylococcus aureus and Cutibacterium acnes, respectively. The DPC film showed 40.78 and 74.04 mm clear zones against S. aureus and C. acnes, respectively. The antibacterial activities of the cLMPC and DPC films were not significantly different from a commercial clindamycin solution. The results of this study suggest that mango peel pectin can be de-esterified and utilized as an LMP and the de-esterified pectin has the potential for use as a film forming agent, similar to cLMP. In addition, the remarkable use of de-esterified mango peel pectin to prepare films, as shown by our study, holds a great promise as an alternative material for anti-bacterial purposes.

Enhancement of Antibacterial Activity of Orange Oil in Pectin Thin Film by Microemulsion.

The purpose of this study was to prepare orange oil microemulsion (ME) and to investigate the antimicrobial activity of film containing orange oil ME. First, surfactants and co-surfactants were screened on their efficiency to form ME using pseudo-ternary phase diagrams. The influences of surfactant and co-surfactant mass ratios were studied and optimized ME-loaded-films were prepared. Then, films containing orange oil ME were characterized by SEM and texture analyzer, and then evaluated for antimicrobial activity against Staphylococcus aureus and Propionibacterium acnes using an agar disc diffusion method. The results showed that Tween 80 as surfactant and propylene glycol as co-surfactant at a 1:1 ratio possessed the maximum ME area. Three ME formulations of ME 20, ME 25, and ME 30, which consisted of 20, 25, and 30% w/v of orange oil were prepared, respectively. All ME formulations showed particle sizes of about 60.26⁻80.00 nm, with broad a polydispersity index of 0.42. The orange oil ME films exhibited higher elastic values than the control. The diameters of inhibition zones for FME 20, FME 25, and FME 30 against P. acnes were 13.64, 15.18, and 16.10 mm, respectively. Only the FME 30 had an antimicrobial activity against S. aureus with 8.32 mm of inhibition zone. Contrarily, the control film had no antimicrobial activity against both bacteria. In conclusion, the present study found that the antibacterial activity of orange oil in pectin thin film could be enhanced by preparing orange oil as an ME before loading into pectin thin film.

Use of Orange Oil Loaded Pectin Films as Antibacterial Material for Food Packaging.

This study aims to develop orange oil loaded in thin mango peel pectin films and evaluate their antibacterial activity against Staphylococcus aureus. The mango peel pectin was obtained from the extraction of ripe Nam Dokmai mango peel by the microwave-assisted method. The thin films were formulated using commercial low methoxy pectin (P) and mango pectin (M) at a ratio of 1:2 with and without glycerol as a plasticizer. Orange oil was loaded into the films at 3% w/w. The orange oil film containing P and M at ratio of 1:2 with 40% w/w of glycerol (P1M2GO) showed the highest percent elongation (12.93 ± 0.89%) and the lowest Young's modulus values (35.24 ± 3.43 MPa). For limonene loading content, it was found that the amount of limonene after the film drying step was directly related to the final physical structure of the film. Among the various tested films, P1M2GO film had the lowest limonene loading content (59.25 ± 2.09%), which may be because of the presence of numerous micropores in the P1M2GO film's matrix. The inhibitory effect against the growth of S. aureus was compared in normalized value of clear zone diameter using the normalization value of limonene content in each film. The P1M2GO film showed the highest inhibitory effect against S. aureus with the normalized clear zone of 11.75 mm but no statistically significant difference. This study indicated that the orange oil loaded in mango peel pectin film can be a valuable candidate as antibacterial material for food packaging.

Effect of Plasticizer Type on Tensile Property and In Vitro Indomethacin Release of Thin Films Based on Low-Methoxyl Pectin.

This study developed the interests of low-methoxyl pectin (LMP) together with plasticizers for the preparation of elastic thin films. The effect of different plasticizer types (glycerol: Gly; sorbitol: Sor; propylene glycol: PG; and polyethylene glycol 300: PEG 300) and concentrations (20⁻40% w/w) on mechanical and thermal properties of LMP films as well as on in vitro release of indomethacin were evaluated. Without any plasticizer, a brittle LMP film with low tensile strength and % elongation at break was obtained. Addition of plasticizers from 20% to 40% caused reduction in the tensile strength and Young's modulus values, whereas percent elongation was increased. Forty percent Gly-plasticized and PG-plasticized films were selected to deliver indomethacin in comparison with non-plasticized film. No significant difference in indomethacin release profiles was displayed between the films. The analysis of indomethacin release model indicated that more than one drug release mechanism from the film formulation was involved and possibly the combination of both diffusion and erosion. Even though indomethacin incorporated in non-plasticized film showed similar release profile, Gly or PG should be added to enhanced film flexibility and decrease film brittleness.