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The application of Artificial Intelligence (AI) has the potential to revolutionize the formulation development of nanomedicine. This study investigated the physicochemical characteristics of progesterone-loaded solid-lipid nanoparticles (PG-SLNs) produced through an emulsification–ultrasonication process, with a focus on demonstrating the efficacy of this controlled preparation method via the Design of Experiments (DoE) and Artificial Neural Networks (ANN). Critical quality factors, including stearic acid, medium chain triglycerides (MCT), Pluronic F-127, and the amount of propylene glycol (PG), were explored using DoE to streamline experimental setups. The concentration of stearic acid was identified as a crucial factor influencing PG-SLN physicochemical properties, impacting particle size (PS), polydispersity index (PDI), zeta potential (ZP), and %drug loading (%DL). Optimal conditions for PS, PDI, ZP, and %DL were identified. DoE revealed acceptable values across multiple runs, and the ANN model demonstrates high prediction accuracy, surpassing Response Surface Methodology (RSM). The selected PG-SLN formulation was tested for transdermal drug delivery, showing improved permeation compared to PG suspension. Loading with limonene further enhances transdermal drug delivery, attributed to limonene’s role as a penetration enhancer. Moreover, the selected PG-SLN formulation was found to be safe and non-toxic to neuronal cells. The combination of DoE and ANN was proposed to enhance predictive ability. This research highlights the potential of PG-SLNs in transdermal drug delivery, emphasizing the role of limonene as a safe and effective enhancer. The study contributes to the growing interest in applying AI tools in pharmaceutical and biomedical fields for improved predictive modeling.

Resveratrol (R) is an antioxidant that helps several aspects of aging skin. However, it is slightly soluble in water and unstable under light exposure, necessitating the use of suitable formulations for improved clinical efficacy. Therefore, this study aimed to prepare R-loaded lipid-based nanocarriers for topical delivery, i.e., nanostructured lipid carriers (NLCs) and nanoemulsions (NEs). R-loaded nanocarrier gels were further prepared to increase R loading. The comparative physical properties and antioxidant activity of nanocarriers were performed in terms of particle size, zeta potential, morphology, rheology, R content, in vitro release, antioxidant activity, cytotoxicity and stability. The results revealed that R was successfully loaded into NLCs and NE gels (NEGs), having different physical properties and antioxidant activity depending on the composition of lipid-based nanocarriers. R could be incorporated into NEs and the aqueous gelling phase, resulting in higher R loading. Furthermore, the gelling network was responsible for pseudoplastic flow behavior. The cumulative amount of R released from NEGs was significantly higher than that from NLCs due to the co-surfactant-like properties of NEGs, which resulted in smaller particle sizes. However, NLCs exhibited significantly more antioxidant activity and less cytotoxicity compared to NEGs. The stability of both nanosystems showed no significant change when stored at refrigerator temperature for over 3 months. In conclusion, the various compositions of lipid-based nanocarriers produced a range of physical properties and antioxidant activity. Nonetheless, these NLCs and NEGs have the potential to be nanocarriers for R, which has antioxidant properties for topical application.

The pharmacopoeial limit test for the impurity 2-aminobutanol (AB) in ethambutol hydrochloride (ETB) relies on florescence measurement using a fluorometer. However, this instrument is often unavailable in many laboratories due to its cost. A novel colorimetric method was therefore developed using genipin, an amine-reactive reagent, to react with AB, producing a blue color. The color intensity was subsequently measured using a more affordable UV-vis spectrophotometer. To overcome matrix effects, the standard addition technique was incorporated. The test effectively detected AB at concentrations as low as 0.125% in ETB, below the compendial limit of 1.0%. The analysis of ETB bulk and tablets showed consistent semi-quantitative results with the USP method. Furthermore, it aligned with green chemistry by eliminating the use of organic solvents and employing safe, naturally derived reagent. In summary, the proposed method provides a reliable, green, and cost-effective alternative for analyzing AB in ETB, ensuring compliance with pharmacopeial standards.

The objective of this study was to develop photo-crosslinkable chitosan methacrylate/polyethylene glycol diacrylate (CSM/PEGDA) hydrogel incorporated with ciprofloxacin (CPx) as antibacterial wound dressing materials. CSM was synthesized from chitosan (CS) and methacrylic acid (MA) at various weight ratio. The hydrogels were prepared using photo-polymerization reaction from CSM and PEGDA using Lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate (LAP) as a photo-initiator. The components were mixed and exposed to UV light to form the hydrogel. Mechanical properties, water content, water absorption, erosion, and water vapor transmission rate were analyzed to determine an appropriate hydrogel. The selected hydrogel was loaded with CPx, then drug loading, drug release, and antibacterial activity against Staphylococcus aureus and Escherichia coli through inhibition zone measurements and time-kill analysis were assessed. CSM was successfully synthesized with the optimal CS:MA weight ratio of 1:2 providing the degree of substitution (DS) of 0.33. The hydrogel composing of CSM:PEGDA:LAP (4.5:1.5:0.5) was most suitable for showing anticipated flexibility and swelling properties. CPx was homogenously loaded into the selected hydrogel and had the ability to prolong drug release via the swollen matrix. The CPx-loaded hydrogel presented potent antimicrobial activity against gram-positive and gram-negative bacteria. Finally, the CPx-loaded hydrogel was developed and proved to be efficient for bacterial-infected wounds.

A new assay of captopril (CTP) tablets was developed based on digital image colorimetry using Ellman’s reagent. For the first time, a facile technique of increasing the analytical path was applied in this work to enhance the sensitivity. For this purpose, the reaction solutions were photographed using a smartphone while they were contained in two 1-cm pathlength cuvettes which were placed side by side. The Red-Green-Blue (RGB) in term of [B/(R+G+B)] was used to plot a standard curve. Compared to using a single cuvette, double cuvettes resulted in more precise analytical signals and better linearity (r2 of 0.9992). Additionally, CTP could be analyzed at low concentrations (2.5–25 µM) with LOD of 0.70 µM and LOQ of 2.13 µM, thus lowering the reagent consumption. The assay was proven to be valid, and it was greener, faster, and more affordable than the pharmacopeial chromatographic method, thereby suitable for pharmaceutical quality control.

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.

Abstract 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.

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy.

This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose–chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization.

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Objective: The aim of the study was to employ electrospinning technology to fabricate aligned nanofibrous scaffolds of polycaprolactone (PCL) containing folic acid (FA) for nerve tissue engineering. Material and Methods: Scanning electron microscopy (SEM) was used to assess the diameter distribution and degree of alignment of the nanofibers. Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD) were used to analyze the chemical and crystalline structures of the scaffold. Additionally, the content and release behavior of FA in the PCL fibrous scaffolds were examined. Finally, the biocompatibility of the scaffolds was evaluated using rat Schwann cells, assessing cell proliferation, alignment, and morphology. Results: The study revealed that the nanofiber diameters ranged from 210.07 to 227.36 nm, and the scaffolds maintained an amorphous form with no effects on their chemical structure following the electrospinning process. The investigation demonstrated that PCL fibers could accommodate FA loading within a range of 99.25-102.49% w/w and that the release profile of FA followed Higuchi model. Moreover, the FA-containing PCL nanofibrous scaffolds significantly enhanced rat Schwann cell proliferation during the initial two days of culture when compared to a normal PCL nanofiber scaffold. The hydrophilic properties of folic acid are thought to have facilitated directional growth along the electrospun nanofibers, contributing to the observed results. Conclusion: Finally, PCL-containing FA nanofibrous scaffolds may be applicable to nerve tissue engineering.

ABSTRACTThe 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.

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.

Boesenbergia rotunda has been used as an antiobesity agent by suppressing adipogenesis. This study aimed to investigate the biological activity of B. rotunda on preadipocyte cells and to evaluate the effectiveness and safety of using B. rotunda extract in a capsaicin-loaded body-firming formulation. The antiadipogenesis of B. rotunda ethanolic extract was evaluated in 3T3-L1 preadipocyte cells. After the application of the B. rotunda extract-loaded body-firming formulation on the skin of volunteers for 28 d, thigh circumference, melanin index, and skin erythema were investigated. The results showed that the ethanolic extract of B. rotunda was not toxic toward 3T3-L1 cells at concentrations lower than 20 µg/mL, with antiadipogenesis of the B. rotunda extract occurring at a concentration of 1 µg/mL. The B. rotunda extract containing panduratin A was mixed with capsaicin body-firming products and successfully permeated into and through the skin. Applying this formulation to the thighs of the volunteers two times a day for 21 days led to a significant reduction in thigh circumference and melanin index. A slight elevation in skin erythema was observed, but there was no significant increase in redness or pain. In conclusion, the B. rotunda extract contained bioactive compounds that inhibited antiadipogenesis. The formulations containing B. rotunda extract and capsaicin showed potential as effective body-firming products.

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.

The study aimed to prepare and evaluate the physicochemical properties of resveratrol (Res)-loaded lipid-nanocarriers including nanostructured lipid carriers (NLCs) and nanoemulsions (NEs). The effects of composition and process parameters on the physicochemical properties were demonstrated. The optimal formulation was selected to prepare the nanocarrier gels. The possible use of the lipid-nanocarriers in gels and their physical appearances was observed by visual inspection. The results showed that small carriers were prepared by homogenization at 6000 rpm for 5 min. The emulsifier system of Tween®80, Span®80 and diethylene glycol monoethyl ether (DGME) provided good physical stability. The NEs could be prepared for Resloaded NE gels (NEGs) with minimum particle size and optimal zeta potential. Alkyl acrylate crosspolymer (PPM) was the best gelling agent in the formulation. Moreover, the blend of NE and gels (NEGs) was easy to spread on the skin with good occlusive property. Thus, these NEGs have a potential to a nanocarrier for topical delivery of Res.

The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. The siRNA delivery system is a crucial factor that influences siRNA therapy’s success. In this study, lipid-based nanoparticles (cationic niosomes) composed of different cholesterol-based cationic lipids were formulated and characterized for delivering siRNA into HER2-overexpressing breast cancer cells. Niosomes containing a trimethylammonium headgroup showed the highest siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1) siRNA nioplex treatment significantly decreased mRNA expression and breast cancer cell growth. Dual-targeted therapy, consisting of treatment with an Mcl-1 siRNA nioplex and trastuzumab (TZ) solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic niosomes were effective nanocarriers for siRNA delivery in breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing breast cancer.

Cellulose acetate nanofibers with different degrees of alignment (randomly aligned (RA), partially aligned (PA), and highly aligned (HA)) were produced using an electrospinning technique. The different degrees of alignment were obtained by adjusting the rotation speed of the collector. Alpha-arbutin (3% w/w) employed as a model water-soluble compound was incorporated into the nanofibers during the fabrication process. The drug release characteristics were investigated using the nanofiber mats with the same size and weight. The prepared nanofibers with different degrees of alignment showed similar physical characteristics, including the fiber diameter, drug loading efficiency and capacity, and molecular form of the drug in the fibers. Interestingly, alpha-arbutin was released from HA nanofibers at a significantly faster rate than the PA and RA nanofibers. Eighty percent of the drug was released into the medium in 1.7, 4.2, and 9.4 min for HA, PA, and RA nanofibers, respectively. The orientation of nanofibers played a crucial role in governing the drug release, probably by creating network meshes with different degrees of entanglement, affecting the diffusion of drug to the external medium. Consequently, this approach can be used as a simple means of achieving immediate-release or fast-acting characteristics of cellulose-based formulations containing a water-soluble drug.

There were two objectives for this study. First, it focused on eight lipids having cholesterol as hydrophobic tails, carbamate linkers, and different polar headgroups. Second, it aimed to study the physicochemical properties of those eight lipids, including DNA binding, size, zeta potential, and the transfection efficiency. Cholesterol-1,2-diaminoethane and tetramethylguanidinium conjugated lipid showed the highest transfection efficacy into human embryonic kidney cells cells. The optimal formulation of this lipid was found to be 1:1 (weight/weight) for cationic lipid/DOPE, and 1:20 for DNA/liposome. GFP expression experiments further revealed that the liposome exhibited higher transfection efficiency under a 10−40% serum condition than LipofectamineTM 2000.

This study aimed to develop microemulsions using poloxamer 124 as a surfactant to improve the skin penetration of finasteride and to investigate the skin penetration pathways of these microemulsions by colocalization techniques using confocal laser scanning microscopy (CLSM). The prepared finasteride-loaded microemulsions had average particle sizes ranging from 80.09 to 136.97 nm with particle size distributions within acceptable ranges and exhibited negative surface charges. The obtained microemulsions could significantly increase the skin penetration of finasteride compared to a finasteride solution. According to the skin penetration pathway evaluation conducted with CLSM, the microemulsions were hair follicle-targeted formulations due to penetration via the transfollicular pathway as a major skin penetration pathway. Additionally, this study found that the microemulsions also penetrated via the intercluster pathway more than via the intercellular pathway and transcellular pathway. The intercluster pathway, intercellular pathway, and transcellular pathway were considered only minor pathways.

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.

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.

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.

The aims of this study were to investigate the skin regeneration potential of bioactive placenta (deer placenta (DP), goat placenta (GP), and porcine placenta (PP)) and fabricate bioactive extract-loaded dissolving microneedles (DMNs) as a dermal delivery approach. The placentas were water-extracted, and the active compounds were evaluated. Bioactivity studies were performed in dermal fibroblasts and keratinocytes. DMNs were fabricated to deliver the potent bioactive placenta extract into the skin. All placental extracts expressed high amounts of protein, growth factors (EGF, FGF, IGF-1 and TGF-β1), and amino acids. These extracts were not toxic to the skin cells, while the proliferation of fibroblast cells significantly increased in a time-dependent manner. GP extract that exhibited the maximum proliferation, migration, and regeneration effect on fibroblast cells was loaded into DMN patch. The suitable physical properties of DMNs led to increased skin permeation and deposition of bioactive macromolecules. Moreover, GP extract-loaded DMNs showed minimal invasiveness to the skin and were safe for application to human skin. In conclusion, placental extracts act as potent bioactive compounds for skin cells, and the highest bioactive potential of GP-loaded DMNs might be a novel approach to regenerate the skin.

Topical film-forming sprays of chlorhexidine gluconate (CHG-FFS) were developed for antiseptic application. Various polymers and solvents were studied for their potential as film-forming polymers and solvent systems, respectively. To produce CHG-FFS, the optimal polymer and solvent were selected, and their physicochemical properties were evaluated. The in vivo evaluation of CHG-FFS was investigated for the satisfaction of the dosage forms, time required for the film formation, film appearance, and adhesion on the skin. Antibacterial activity was also studied in vitro and in vivo. The optimized formulation was assessed for the in vitro cell line evaluations of the cytotoxicity and wound healing. The results demonstrate that Eudragit® S100, Eudragit® L100, and polyvinyl alcohol (PVA) have the ability to be used as film-forming polymers in an ethanolic solution. A clear and flexible film was obtained from transparent homogenous solutions of CHG-FFS after actuation. They generated the fast thin film formation on the skin with the satisfaction of the dosage forms. Furthermore, the formulations inhibited the growth of Staphylococcus aureus in vitro and provided antiseptic activity in vivo. However, PVA was found to be an optimal film-forming polymer for promoting CHG adhesion on the skin. The CHG-FFS obtained from the PVA also provided a CHG film, which was non-toxic to human skin cells and did not interfere with the wound healing process. Therefore, the developed CHG-FFS could be a promising candidate for topical antiseptic application.

Doxorubicin (Dox) is known for its potential to deliver desirable anticancer effects against various types of cancer including colorectal cancer. However, the adverse effects are serious. This study aimed to synthesize polyethylene glycol diacrylate (PEGDA)/acrylic acid (AA)-based nanoparticles (PEGDA/AA NPs) for Dox delivery to colorectal cancer cells. The NPs were synthesized using free-radical polymerization reaction using the monomers PEGDA and AA with their physical properties, drug loading and release, biocompatibility, and anticancer effect evaluated. The NPs were spherical with a size of around 230 nm, with a 48% Dox loading efficiency and with loading capacity of 150 µg/mg. Intriguingly, the NPs had the ability to prolong the release of Dox in vitro over 24 h and were non-toxic to intestinal epithelial cells. Dox-loaded PEGDA/AA NPs (Dox-NPs) were able to effectively kill the colorectal cancer cell line (HT-29) with the Dox-NPs accumulating inside the cell and killing the cell through the apoptosis pathway. Overall, the synthesized PEGDA/AA NPs exhibit considerable potential as a drug delivery carrier for colon cancer-directed, staged-release therapy.

The optimal design of novel microneedles (MNs) for the ocular delivery system is necessary and useful for improving the effectiveness of medication. The objective of this study was to design and develop the optimal fluconazole (FLUZ)-microemulsions (MEs)-loaded two-layered dissolving MNs as a potential treatment for fungal eye infection. The experimental designs using the simplex-lattice design were used to select the optimal formulation. The two-layered dissolving MNs were fabricated from 3% chitosan and 20% polyvinyl alcohol (PVA) in a weight ratio of 1:4 as an outer layer and FLUZ-loaded MEs containing eugenol, tween 80, PEG400, and water as an inner layer. The physical appearance, mechanical properties, penetration ability, dissolution time, in vitro/ex vivo ocular drug delivery, and antifungal activity were evaluated. From the results, the optimal two-layered dissolving MNs exhibited good physical properties, complete insertion, minimally invasive ocular tissue, and high stability at 4 °C and 25 °C for 3 months. Moreover, the optimal two-layered dissolving MNs showed significantly higher FLUZ permeation into the ocular tissue than other formulations, while providing highly potential antifungal activity. In conclusion, the optimal MEs-loaded two-layered MNs’ formulation had appropriate properties for ocular delivery of FLUZ, resulting in an improvement of fungal keratitis treatment.

The objective of this study was to develop novel water-based drug-in-adhesive pressure-sensitive adhesives (PSAs) patches for the transdermal delivery of ketoprofen, employing poly(N-vinylpyrrolidone-co-acrylic acid) copolymer (PVPAA) and poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) as the main components. The polymers were crosslinked with tartaric acid and dihydroxyaluminium aminoacetate using various polymer ratios. Ketoprofen was incorporated into the PVPAA/PMVEMA PSAs during the patch preparation. The physicochemical properties, adhesive properties, drug content, release profile, and skin permeation of the patches were examined. Moreover, the in vivo skin irritation and skin adhesion performance in human volunteers were evaluated. The patches prepared at a weight ratio of PVPAA/PMVEMA of 1:1 presented the highest tacking strength, with desirable peeling characteristics. The ketoprofen-loaded PVPAA/PMVEMA patches exhibited superior adhesive properties, compared to the commercial patches, because the former showed an appropriate crosslinking and hydrating status with the aid of a metal coordination complex. Besides, the permeated flux of ketoprofen through the porcine skin of the ketoprofen-loaded PVPAA/PMVEMA patches (4.77 ± 1.00 µg/cm2/h) was comparable to that of the commercial patch (4.33 ± 0.80 µg/cm2/h). In human studies, the PVPAA/PMVEMA patches exhibited a better skin adhesion performance, compared with the commercial patches, without skin irritation. In addition, the patches were stable for 6 months. Therefore, these novel water-based PSAs may be a potential adhesive for preparing drug-in-adhesive patches.

Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using chemotherapeutic agents along with gene therapy could be a potential strategy for cancer management, which not only improves therapeutic efficacy but also decreases untoward effects from dose reduction. In this study, a cationic niosome containing plier-like cationic lipid B was used to convey siRNA against anti-apoptotic mRNA into MCF-7 and MDA-MB-231 cells. Mcl-1 silencing markedly decreased the viability of MCF-7 cells and triggered apoptosis. Moreover, computer modeling suggested that the combination of doxorubicin (Dox) and Mcl-1 siRNA exhibited a synergistic relationship and enabled a dose reduction of each agent at 1.71 and 3.91 folds, respectively, to reach a 90% inhibitory effect when compared to single-agent treatments. Synergistic antitumor activity was further verified in a 3D spheroid culture which revealed, in contrast to single-agent treatment, the combination markedly decreased spheroid volume over time. Together, the combination therapy between Mcl-1 silencing and Dox exhibits a synergistic effect that may be exploited for novel breast cancer treatment.

This study aimed to develop ultradeformable liposomes (ULs) with fatty acids, namely, oleic, linoleic, and linolenic acid, to improve the skin penetration of rosmarinic acid. This study also investigated the vesicle-skin interaction and skin penetration pathway of ULs with fatty acids using the co-localization technique of multifluorescently labeled particles. The prepared ULs were characterized in terms of size, surface charge, size distribution, shape, % entrapment efficiency (% EE), and % loading efficiency (% LE). The prepared ULs with fatty acids had an average particle size between 50.37 ± 0.3 and 59.82 ± 17.3 nm with a size distribution within an acceptable range and exhibited a negative surface charge. The average % EE and % LE were 9 and 24.02, respectively. The in vitro skin penetration study found that ULs with oleic acid could significantly increase the skin penetration of rosmarinic acid compared to ULs. According to confocal laser scanning microscopy observations, this study suggested that UL vesicles attach to the skin before releasing the entrapped drug to penetrate the skin. These findings suggested that ULs with oleic acid penetrated the skin via the transfollicular pathway as a major penetration pathway.

This study aimed to evaluate the patient-friendly methods that are used in the delivery of hydrophilic macromolecules into deep skin layers, in particular, the combination of microneedles patch (MNs patch) and low-frequency sonophoresis (SN). The hydrophilic macromolecule drug fluorescein isothiocyanate (FITC)-dextrans (FD-4: MW 4.4 kDa) was used as the model drug in our experimental design. In this study, excised porcine skin was used to investigate and optimize the key parameters that determine effective MNs- and SN-facilitated FD-4 delivery. In vitro skin permeation experiments revealed that the combination of MNs patch with SN had a superior enhancing effect of skin permeation for FD-4 compared to MNs alone, SN alone or untreated skin, respectively. The optimal parameters for the combination of MNs and SN included the following: 10 N insertion force of MNs, 4 W/cm2 SN intensity, 6 mm radiation diameter of the SN probe, 2 min application time, and the continuous mode duty cycle of SN. In addition, vertical sections of skin, clearly observed under a confocal microscope, confirmed that the combination of MNs and SN enhanced permeation of FD-4 into the deep skin layers. These studies suggest that the combination of MNs and SN techniques could have great potential in the delivery of hydrophilic macromolecules into deep skin.