Statistical-Based Optimization of Modified Mangifera indica Fruit Starch as Substituent for Pharmaceutical Tableting Excipient.

This study aimed to optimize modified starch from Mangifera indica (mango) fruit using acid hydrolysis and pre-gelatinization via computer-assisted techniques as a substituent for pharmaceutical tableting excipients. The hydrolysis and microwave-assisted pre-gelatinization time and temperature were optimized using a three-level factorial design. The modified starches were characterized for flowability, compressibility, and swelling properties. It was found that all parameters fit a quadratic model, which can be used to predict the properties of the modified starch. The optimized hydrolysis reaction was 3.8 h at 56.4 °C, while the pre-gelatinization reaction was 3 min at 150 °C. Structural changes were found, ascertaining that starch modification was successful. The optimized hydrolyzed starch showed superior properties in relative to unmodified M. indica fruit starch and comparable characteristics to conventional excipients. The optimized pre-gelatinized starch presented an excellent enhancement in the flow and compression properties, with %swelling greatly augmented 3.95-fold and 1.24-fold compared to unmodified starch and SSG, respectively. Additionally, the pre-gelatinized starch presented comparable binding effect, while the hydrolyzed powder had reduced binding capacity due to shorter chains. The findings revealed that the use of software-assisted design of experiment facilitated a data-driven approach to optimize the modifications. The optimized modified mango starch demonstrated potential as a multifunctional excipient, capable of functioning as binder, disintegrant, and diluent.

Computational Designed and Optimized Liposomal Curcumin-Embedded Bifunctional Cross-Linked Hydrogels for Wound Healing.

Curcumin (CUR) bifunctional cross-linked nanocomposite hydrogels are presented as an efficient method for CUR delivery in wound healing. CUR-loaded liposomes (CUR-Ls) were optimized using the Box-Behnken design to augment particle size, size distribution, zeta potential, and CUR concentration. The antioxidant activity and cytotoxicity of CUR-Ls were assessed. Hyaluronic acid (HA)/poly(vinyl alcohol) (PVA) hydrogels were optimized with a central composite design; then, poly(N-vinylpyrrolidone-co-itaconic acid) (PNVP-ITA) was synthesized to enrich the properties of the hydrogels. The drug release kinetics of the CUR-L@HA/PVA/PNVP-ITA hydrogels were studied. Skin recovery was investigated in vivo on rat dorsal skin. The optimized CUR-Ls were constructed from 2.7% Tween® 20, 0.04% oleic acid, and 8.1% CUR, yielding nano-CUR-L with a narrow size distribution, negative surface charge, and CUR content of 19.92 ± 0.54 µg/mg. CUR-Ls improved the antioxidant effects of CUR. The optimized hydrogel contained 5% HA and 10% PVA. PNVP-ITA improved the properties of the hydrogels via enhanced cross-linking. CUR-Ls exhibited a more rapid release than CUR, whereas the hydrogels enhanced CUR release via a diffusion-controlled mechanism. CUR-L@HA/PVA/PNVP-ITA hydrogels improved the skin recovery rate compared to the commercial patch after 5 days. Therefore, the optimized CUR-L@HA/PVA/PNVP-ITA hydrogels facilitated skin recovery and could be a promising nanocomposite for wound dressings.

The Artificial Intelligence-Powered New Era in Pharmaceutical Research and Development: A Review.

Currently, artificial intelligence (AI), machine learning (ML), and deep learning (DL) are gaining increased interest in many fields, particularly in pharmaceutical research and development, where they assist in decision-making in complex situations. Numerous research studies and advancements have demonstrated how these computational technologies are used in various pharmaceutical research and development aspects, including drug discovery, personalized medicine, drug formulation, optimization, predictions, drug interactions, pharmacokinetics/ pharmacodynamics, quality control/quality assurance, and manufacturing processes. Using advanced modeling techniques, these computational technologies can enhance efficiency and accuracy, handle complex data, and facilitate novel discoveries within minutes. Furthermore, these technologies offer several advantages over conventional statistics. They allow for pattern recognition from complex datasets, and the models, typically developed from data-driven algorithms, can predict a given outcome (model output) from a set of features (model inputs). Additionally, this review discusses emerging trends and provides perspectives on the application of AI with quality by design (QbD) and the future role of AI in this field. Ethical and regulatory considerations associated with integrating AI into pharmaceutical technology were also examined. This review aims to offer insights to researchers, professionals, and others on the current state of AI applications in pharmaceutical research and development and their potential role in the future of research and the era of pharmaceutical Industry 4.0 and 5.0.

Multiple strategies approach: A novel crosslinked hydrogel forming chitosan-based microneedles chemowrap patch loaded with 5-fluorouracil liposomes for chronic wound cancer treatment.

Untreated or poorly managed chronic wounds can progress to skin cancer. Topically applied 5-fluorouracil (5-FU), a nonspecific cytostatic agent, can cause various side effects. Its high polarity also results in low cell membrane affinity and bioavailability. Hydrogel, used for its occlusive effect, is one platform for treating chronic wounds combined with PEGylated liposomes (LPs), developed to increase drug-skin affinity. This research aimed to develop a novel hydrogel forming chitosan-based microneedles (HFM) chemowrap patch containing 5-FU PEGylated LPs, improving 5-FU efficiency for pre-carcinogenic and carcinogenic skin lesions. The results indicated that the 5-FU-PEGylated LPs-loaded HFM chemowrap patch exhibited desirable physical and mechanical characteristics with complete penetration ability. Furthermore, in vivo skin permeation studies demonstrated the highest percentage of 5-FU permeated the skin (42.06 ± 11.82 %) and skin deposition (75.90 ± 1.13 %) compared to the other treatments, with demonstrated superior percentages of complete wound healing in in vivo (47.00 ± 5.77 % wound healing at day 7) and in NHF cells (92.79 ± 7.15 % at 48 h). Furthermore, 5-FU-PEGylated LPs-loaded HFM chemowrap patches exhibit efficient anticancer activity while maintaining safety for normal cells. The results also show that the developed formulation of a 5-FU-PEGylated LPs-loaded HFM chemowrap patch could enhance apoptosis higher than that of the 5-FU solution. Consequently, 5-FU PEGylated LPs-loaded HFM chemowrap patch represented a promising drug delivery approach for treating pre-carcinogenic and carcinogenic skin lesions.

Development and characterization of curcumin nanosuspension-embedded genipin-crosslinked chitosan/polyvinylpyrrolidone hydrogel patch for effective wound healing.

This study investigated the development of a genipin-crosslinked chitosan (CS)-based polyvinylpyrrolidone (PVP) hydrogel containing curcumin nanosuspensions (Cur-NSs) to promote wound healing in an excisional wound model. Cur-NSs were prepared, and a simplex centroid mixture design was employed to optimize hydrogel properties for high water absorption, degree of crosslinking, and sufficient toughness. The in vivo wound healing effect was tested in Wistar rats. The optimized hydrogel consisted of a 70:30 ratio of CS:PVP, crosslinked with a 2 % w/w genipin solution. It exhibited high swelling capability (486 %) while maintaining solidity, robustness, and durability. Incorporating 5 % w/w Cur-NSs resulted in a more compact structure, although with a reduction in swelling properties. The release kinetics of Cur from the hydrogel followed the Korsmeyer-Peppas Fickian diffusion model. In vitro biocompatibility studies demonstrated that the hydrogel was non-toxic to skin fibroblast cells. The in vivo experiment revealed a desirable wound healing rate with over 80 % recovery by day 7. Cur-NSs likely aided wound healing by reducing the inflammatory response and stimulating fibroblast proliferation. Additionally, the CS-based hydrogel provided a moist wound environment with hydration and gas transfer, further accelerating wound closure. These findings suggest that the Cur-NS-embedded hydrogel shows promise as a wound dressing material.

Development and Optimization of Andrographis paniculata Extract-Loaded Self-Microemulsifying Drug Delivery System Using Experimental Design Model.

The objectives of this study were to develop an optimized formulation for an Andrographis paniculata extract (AGPE)-loaded self-microemulsifying drug delivery system (SMEDDS) using an experimental design and evaluate the characteristics of the developed SMEDDS. The solubility of andrographolide (AGP) in various solvents was investigated. The pseudo-ternary phase was constructed to provide an optimal range for each component to form microemulsions (MEs). The formulation was optimized using an I-optimal design mixture type, where the physical stability, droplet size, polydispersity index, and zeta potential were examined. Soft capsules of the optimized AGPE-loaded SMEDDS were manufactured. The dissolution and ex vivo membrane permeation were studied. Oleic acid, Tween® 80, and PEG 400 were the best solubilizers for AGP. The promising surfactant to co-surfactant ratio to generate ME was 3:1. The optimized SMEDDS contained 68.998% Tween® 80, with 13.257% oleic acid and 17.745% PEG 400. The assayed content of AGP, uniformity of dosage unit, and stability complied with the expected specifications. The dissolution and membrane permeability of AGPE-loaded SMEDDS was significantly improved from the A. paniculata extract (p < 0.05). All in all, the developed optimized AGPE-loaded SMEDDS was proven to contain optimal composition and AGP content where a stable ME could spontaneously be formed with enhanced delivery efficacy.

Photodynamic Antibacterial Therapy of Gallic Acid-Derived Carbon-Based Nanoparticles (GACNPs): Synthesis, Characterization, and Hydrogel Formulation.

Carbon-based nanoparticles (CNPs) have gained recognition because of their good biocompatibility, easy preparation, and excellent phototherapy properties. In biomedicine applications, CNPs are widely applied as photodynamic agents for antibacterial purposes. Photodynamic therapy has been considered a candidate for antibacterial agents because of its noninvasiveness and minimal side effects, especially in the improvement in antibacterial activity against multidrug-resistant bacteria, compared with conventional antibiotic medicines. Here, we developed CNPs from an active polyhydroxy phenolic compound, namely, gallic acid, which has abundant hydroxyl groups that can yield photodynamic effects. Gallic acid CNPs (GACNPs) were rapidly fabricated via a microwave-assisted technique at 200 °C for 20 min. GACNPs revealed notable antibacterial properties against Gram-positive and Gram-negative bacteria, including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The minimum inhibitory concentrations of GACNPs in S. aureus and E. coli were equal at approximately 0.29 mg/mL and considerably lower than those in gallic acid solution. Furthermore, the GACNP-loaded hydrogel patches demonstrated an attractive photodynamic effect against S. aureus, and it was superior to that of Ag hydrofiber®, a commercial material. Therefore, the photodynamic properties of GACNPs can be potentially used in the development of antibacterial hydrogels for wound healing applications.

Fabrication of controlled-release polymeric microneedles containing progesterone-loaded self-microemulsions for transdermal delivery.

Progesterone (PG) has been approved for hormone replacement therapy to mitigate the risk of endometrial carcinoma. However, there has been a lack of success in oral PG due to its rapid degradation. Transdermal PG has advantages but lacks efficacy due to its poor solubility (Log p = 3.9). Therefore, this study aimed to evaluate how combining self-microemulsifying drug delivery systems (SMEDDS) and polymeric microneedles (MNs) could improve the transdermal delivery of PG in a controlled-release manner. Among PG-SMEDDS, PG-SME5 was selected for its desirable properties and stability. The two-layer polymeric MNs formulation incorporating PG-SME5 (PG-SMEDDS-tMNs) was formulated from aqueous blends of polymers as a first layer and 20% PCL as a second layer. It successfully penetrated neonatal porcine skin with the dissolution of the first layer observed within 15 min after application. In vitro skin permeation revealed that the percentage of PG which permeated the skin over 82 h using PG-SMEDDS-tMNs was higher than a PG-suspension and PG-SMEDDS. The Higuchi kinetic showed controlled release over 15 days of PG from PG-SMEDDS-tMNs. These studies suggested that incorporating PG-SMEDDS into controlled-release two-layer polymeric MNs could be a promising approach for improving the transdermal delivery of PG.

Antibody-decorated chitosan-iodoacetamide-coated nanocarriers for the potential delivery of doxorubicin to breast cancer cells.

Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.

Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers.

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 µg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

Optimization of In Situ Gel-Forming Chlorhexidine-Encapsulated Polymeric Nanoparticles Using Design of Experiment for Periodontitis.

Periodontitis is a chronic inflammatory disease of the gums caused by pathogenic microorganisms damaging and destroying periodontal tissues. Chlorhexidine digluconate (CHX) is a commonly used antimicrobial agent for the treatment of periodontitis. However, it has many drawbacks, such as toxicity due to the high dosage required, low prolonged release, and low adhesion in the periodontal pocket. The objective of this study was to develop and optimize CHX-encapsulated polymeric nanoparticles (NPs) loaded into in situ gel-forming (ISGF) using design of experiment (DoE) to improve the treatment of periodontitis and overcome these limitations. CHX-NPs were optimized from 0.046%w/v chitosan, 0.05%w/w gelatin, and 0.25%w/w CHX. After that, the optimized of CHX-NPs was loaded into a thermosensitive ISGF, which was a mixture of 15%w/v Poloxamer 407 and 1% hydroxypropyl methylcellulose (HPMC). The optimized CHX-NPs, loaded into ISGF, was evaluated by measuring gelling temperature and time, pH, viscosity, compatibility, in vitro drug release, antibacterial activity, cytotoxicity, and stability. The results showed that the size, PDI, and zeta potential of optimized CHX-NPs were 53.07±10.17 nm, 0.36±0.02, and 27.63±4.16 mV, respectively. Moreover, the optimized ISGF loading CHX-NPs showed a gelling temperature at 34.3±1.2°C within 120.00±17.32 s with a pH value of 4.06. The viscosity of the formulations at 4°C was 54.33±0.99 cP. The DSC and FTIR showed no interaction between ingredients. The optimal formulations showed a prolonged release of up to 7 days while providing potential antibacterial activity and were safe for normal gingival fibroblast cells. Moreover, the formulations had high stability at 4°C and 25°C for 3 months. In conclusion, the study achieved the successful development of ISGF loading CHX-NPs formulations for effectiveness use in periodontal treatment.

Chitosan capped-gold nanoparticles as skin penetration enhancer for small molecules: A study in porcine skin.

Skin is considered one of the most convenient sites for drug administration. The present study evaluated the effect of gold nanoparticles stabilized by chitosan (CS-AuNPs) and citrate ions (Ci-AuNPs) on skin permeation of sodium fluorescein (NaFI) and rhodamine b base (RhB) as small model hydrophilic and lipophilic permeants, respectively. CS-AuNPs and Ci-AuNPs were characterized by transmitted electron microscopy (TEM) and dynamic light scattering (DLS). Skin permeation was investigated using porcine skin with diffusion cells and confocal laser scanning microscopy (CLSM). The CS-AuNPs and Ci-AuNPs were spherical-shaped nanosized particles (38.4 ± 0.7 and 32.2 ± 0.7 nm, respectively). The zeta potential of CS-AuNPs was positive (+30.7 ± 1.2 mV) whereas that of Ci-AuNPs was negative (-60.2 ± 0.4 mV). The skin permeation study revealed that CS-AuNPs could enhance the permeation of NaFI with enhancement ratio (ER) of 38.2 ± 7.5, and the effect was superior to that of Ci-AuNPs. CLSM visualization suggested that skin permeation was enhanced by improving the delivery through the transepidermal pathway. However, the permeability of RhB, a lipophilic molecule, was not significantly affected by CS-AuNPs and Ci-AuNPs. Moreover, CS-AuNPs had no cytotoxic toward human skin fibroblast cells. Therefore, CS-AuNPs are a promising skin permeation enhancer of small polar compounds.

Fabrication of polyvinyl pyrrolidone-K90/Eudragit RL100-based dissolving microneedle patches loaded with alpha-arbutin and resveratrol for skin depigmentation.

Alpha-arbutin (AA) and resveratrol (Res) are widely used in skin-lightening products. However, current topical formulations have minimal skin-lightening effects due to the low absorption and poor solubility of these active compounds. This study investigated the efficacy and safety of using dissolving microneedle (DMN) patches to improve the delivery of AA and Res for skin depigmentation. The DMN patches (F0-F3) fabricated from polyvinyl pyrrolidone-K90 (PVP-K90)/Eudragit RL100 blends successfully penetrated excised porcine skin and showed sufficient mechanical strength to resist compression forces. Loading DMNs with 10% AA and 2% Res at a ratio of 5 : 1 (F3) resulted in a synergistic interaction between the drugs with desirable dissolving ability, drug loading, and stability. Furthermore, both in vitro and in vivo studies revealed that the use of F3 DMN patches successfully enhanced the intradermal delivery of AA and Res over a 24 h period, with the delivered amount being higher (∼2.6 times) than that provided by a cream formulation (P < 0.05). After removing the DMN patches, the mice's skin was spontaneously and completely resealed within 12 h. In clinical studies, F3 DMN patches slightly decreased the melanin index of the participants without causing skin irritation or erythema at any time during the 24 h period when the patches were applied (P < 0.05). Moreover, application of the patches for 24 h was not found to affect skin hydration, transepidermal water loss, or skin elasticity. Therefore, AA/Res-loaded DMN patches could offer a promising approach for the effective local delivery of cosmetic agents for skin depigmentation.

Bioinspired ketoprofen-incorporated polyvinylpyrrolidone/polyallylamine/ polydopamine hydrophilic pressure-sensitive adhesives patches with improved adhesive performance for transdermal drug delivery.

Inspired by the natural mussel adhesive mechanism, three different materials-polydopamine (PDA), polyvinylpyrrolidone (PVP), and polyallylamine (PAM)-were used to make innovative pressure-sensitive adhesives (PSAs) for transdermal delivery of ketoprofen. PDA was synthesized under alkaline conditions using a self-polymerization reaction and was exploited as a cross-linking agent due to its biocompatibility. The adhesive performance, physicochemical properties, drug content, and drug permeation through the skin were examined. Moreover, in vivo skin irritation and skin adhesion performance were investigated. PVP/PAM/PDA PSAs showed a significantly higher adhesion to human skin compared with commercial patches owing to the interaction between the catechol groups presented on the patches and the skin. In addition, the patches were stable for six months. Consequently, the PVP/PAM/PDA patches exhibited outstanding tissue adhesiveness, enabling universal tissue adherence while causing no skin tissue irritation or inflammatory reaction.

Mussel-inspired poly(hydroxyethyl acrylate-co-itaconic acid)-catechol/hyaluronic acid drug-in-adhesive patches for transdermal delivery of ketoprofen.

This research aimed to create new hydrophilic drug-in-adhesive patches for transdermal drug delivery. Poly(hydroxyethyl acrylate-co-itaconic acid)-catechol (PHI-cat) and hyaluronic acid (HA) were used as main components in the pressure-sensitive adhesive. Citric acid and aluminium hydroxide were exploited as crosslinking agents and ketoprofen was employed as a model delivering compound. The adhesive performance, physicochemical properties, drug-polymer interaction, drug crystallization, drug content, drug permeation through the skin, and coordination polymer network of the patches were investigated. In addition, skin irritation and adhesion potential in human subjects were assessed. Due to the ability of catechol groups to form interaction with the skin tissue, the patches containing PHI-cat and HA offered a considerably greater adhesion ability to human skin compared with the patches without catechol and commercial patches. Furthermore, the patches had good physical and chemical stability. Therefore, these catechol-functionalized patches may be potential transdermal drug delivery systems with excellent adhesive properties for the delivery of a drug through the skin.

The utilization of mangosteen pericarp extract for anticoccidial drug replacement in broiler feed.

The use of anticoccidial drugs in broilers has led to concerns, especially the drug residues in meat and the occurrence of drug resistance. This study aimed to extract, standardize, quantify and utilize mangosteen pericarp extract (MPE) containing α-mangostin as a replacement for anticoccidial drugs in broiler feed. The pericarp was acquired from different areas of Thailand and used for extraction and standardization. The antioxidant activity of the extract was evaluated. The extract was formulated into granules, and the flowability and stability of the granules were assessed. The MPE formulation was added to the broiler feed and then fed to the broilers that were infected with Eimeria tenella. The growth rate and intestinal lesion score (post-mortem) of the broilers were assessed. The pericarp obtained passed the identification test and phytochemical analyses. The active compound, α-mangostin, was best extracted using 95% ethanol. The MPE had superior antioxidant activity compared to standard antioxidants. Granules of the extract formulated with Avicel® PH102 provided desirable flowability and stability. The broilers fed with the feed containing 500 mg/kg α-mangostin showed a similar growth rate and post-mortem lesion score compared with the control group and those that received feed containing 60 mg/kg salinomycin. Our findings demonstrated that MPE with a high content of the active compound could be developed and used in place of anticoccidial drugs in the broiler feed.

In Vitro Biological Activity and In Vivo Human Study of Porcine-Placenta-Extract-Loaded Nanovesicle Formulations for Skin and Hair Rejuvenation.

Porcine placenta extract (PPE) contains many water-soluble macromolecular compounds, such as proteins and growth factors, which have limited transportation through the skin. This study aimed to assess the effect of porcine-placenta-extract (PPE)-loaded nano-transdermal systems for skin repair and hair growth promotion. The potentials of the nanoformulation for cytotoxicity, cell proliferation, intracellular reactive oxygen species (ROS) reduction, lipoxygenase inhibition, intracellular inflammatory cytokine reduction, and cell aggregation were evaluated. PPE-entrapped niosome nanovesicles were produced by thin-film hydration and probe-sonication methods, followed by incorporation in a skin serum formulation. The physicochemical properties of the formulation were examined, and the efficacy of the serum formulation was elucidated in humans. The results showed that PPE had no toxicity and was able to induce cell growth and cell aggregation. In addition, PPE significantly decreased intracellular ROS, inhibited lipoxygenase activity, and reduced the production of intracellular tumor necrosis factor-α. In the in vivo human study, the PPE nanovesicles-loaded serum could improve skin properties by increasing skin hydration. Moreover, it was capable of promoting hair growth by increasing hair elongation and melanin index after application for one month. Consequently, the PPE nanovesicles-loaded serum was effective for skin anti-aging and hair rejuvenation.

siRNA Targeting Mcl-1 Potentiates the Anticancer Activity of Andrographolide Nanosuspensions via Apoptosis in Breast Cancer Cells.

Breast cancer is the second leading cause of cancer-related death in the US. However, recurrence is frequently found despite adjuvant therapy being available. Combination therapy with cytotoxic drugs and gene therapy is being developed to be a new promising cancer treatment strategy. Introducing substituted dithiocarbamate moieties at the C12 position of andrographolide (3nAG) could improve its anticancer selectivity in the MCF-7 breast cancer cell line. However, its hydrophobicity is one of its main drawbacks. This work successfully prepared 3nAG nanosuspension stabilized with the chitosan derivative NSC (3nAGN-NSC) to increase solubility and pharmacological effectiveness. siRNAs have emerged as a promising therapeutic alternative for interfering with particular mRNA. The 3nAGN-NSC had also induced Mcl-1 mRNA expression in MCF-7 human breast cancer cells at 8, 12, and 24 h. This indicates that, in addition to Mcl-1 silencing by siRNA (siMcl-1) in MCF-7 with substantial Mcl-1 reliance, rationally devised combination treatment may cause the death of cancer cells in breast cancer. The Fa-CI analysis showed that the combination of 3nAGN-NSC and siMcl-1 had a synergistic effect with a combination index (CI) value of 0.75 (CI < 1 indicating synergistic effects) at the fractional inhibition of Fa 0.7. The synergistic effect was validated by flow cytometry, with the induction of apoptosis as the mechanism of reduced cell viability. Our findings suggested the rational use of 3nAGN-NSC in combination with siMcl-1 to kill breast cancer cells.

Formulation and Optimal Design of Dioscorea bulbifera and Honey-Loaded Gantrez®/Xyloglucan Hydrogel as Wound Healing Patches.

Hydrogel patches are some of the most effective dressings for wound healing. In this study, the Gantrez® S-97 (Gan)/xyloglucan (XG) hydrogel patches were formulated by using a full central composite design (CCD). The optimized hydrogel patches consisted of 17.78% w/w of Gan and 0.1% w/w of XG. Honey and D. bulbifera extract were loaded in the Gan/XG hydrogel patches. The physical properties of the hydrogel patches, including water content, water absorption, rate of water vapor transmission, and mechanical properties, were examined. The D. bulbifera extract/honey-loaded patch exhibited a higher value of water absorption, tensile strength, and elongation than the honey-loaded patch and the unloaded patch, respectively. The biological activities of the patches were also investigated. All hydrogel patches protected wounds from external bacterial infection. The D. bulbifera extract/honey-loaded patch exhibited stronger antioxidant activity than the honey-loaded patch and the unloaded patch. Besides, all the hydrogel patches with concentrations of 0.5-2.5 mg/mL showed that they were nontoxic to fibroblast cells. The combination of D. bulbifera extract and honey in the patch affected fibroblast proliferation. In addition, all Gan/XG hydrogel patches significantly induced recovery of the scratch area. Therefore, the Gan/XG hydrogel patches could be candidates as wound dressings.

Maleimide-functionalized carboxymethyl cellulose: A novel mucoadhesive polymer for transmucosal drug delivery.

The objective of this research was to develop a novel mucoadhesive polymer for drug delivery applications based on N-(2-aminoethyl) maleimide-functionalized carboxymethyl cellulose in which the weight ratios of the materials were tuned to explore the condition providing the highest maleimide content on the polymer. The polymers were synthesized from N-(2-aminoethyl) maleimide that was conjugated to carboxymethyl cellulose with their mucoadhesive properties examined by tensile testing, rheology, and flow-through analysis and their biocompatibilities evaluated on the human gingival fibroblast cell line (HGF-1). The anti-inflammatory drug benzydamine was loaded into mucoadhesive-polymer-based tablets and used to demonstrate the application of the synthesized polymer. The polymer exhibited superior mucoadhesive capability compared to carboxymethyl cellulose through the interaction between maleimide moiety and mucin. The functionalized polymer also possessed the ability to control the release of benzydamine with Higuchi's release model and was proven to be a potential candidate in mucoadhesive drug delivery.