Development of itraconazole ocular delivery system using ß-cyclodextrin complexation incorporated into dissolving microneedles for potential improvement treatment of fungal keratitis.

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using ß-cyclodextrin (ß-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the ß-CD was -5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using ß-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.

Bioavailability enhancement of sildenafil citrate via hydrogel-forming microneedle strategy in combination with cyclodextrin complexation.

Sildenafil citrate (SIL) as a first-line treatment for erectile dysfunction is currently reported to have poor solubility and bioavailability. Moreover, SIL undergoes first-pass metabolism when taken orally and its injection can lead to discomfort. In this study, we introduce a novel transdermal delivery system that integrates hydrogel-forming microneedles with the inclusion complex tablet reservoir. The hydrogel-forming microneedle was prepared from a mixture of polymers and crosslinkers through a crosslinking process. Importantly, the formulations showed high swelling capacity (>400 %) and exhibited adequate mechanical and penetration properties (needle height reduction < 10 %), penetrating up to five layers of Parafilm® M (assessed to reach the dermis layer). Furthermore, to improve the solubility of SIL in the reservoir, the SIL was pre-complexed with ß-cyclodextrin. Molecular docking analysis showed that SIL was successfully encapsulated into the ß-cyclodextrin cavity and was the most suitable conformation compared to other CD derivatives. Moreover, to maximize SIL delivery, sodium starch glycolate was also added to the reservoir formulation. As a proof of concept, in vivo studies demonstrated the effectiveness of this concept, resulting in a significant increase in AUC (area under the curve) compared to that obtained after administration of pure SIL oral suspension, inclusion complex, and Viagra® with relative bioavailability > 100 %. Therefore, the approach developed in this study could potentially increase the efficacy of SIL in treating erectile dysfunction by being non-invasive, safe, avoiding first-pass metabolism, and increasing drug bioavailability.

Ginger potency on the prevention and treatment of breast cancer.

BACKGROUND: Cancer is a type of disease caused by the uncontrolled growth of abnormal cells that can destroy body tissues. The use of traditional medicine naturally uses plants from ginger with the maceration method. The ginger plant is a herbaceous flowering plant with the Zingiberaceacea group. METHODS: This study uses the literature review method by reviewing 50 articles from journals and databases. RESULTS: A review of several articles, namely ginger has bioactive components such as gingerol. Ginger is used as a treatment in complementary therapies using plants. Ginger is a strategy with many benefits and functions as a nutritional complement to the body. This benefit has shown the effect of anti-inflammatory, antioxidant, and anticancer against nausea and vomiting due to chemotherapy in breast cancer. CONCLUSION: Anticancer in ginger is shown by polyphenols associated with anti-metastatic, anti-proliferative, antiangiogenic, anti-inflammatory, cell cycle arrest, apoptosis, and autophagy. Therefore, consuming ginger regularly affects natural herbal therapy with the prevention and treatment of breast cancer and serves as a prevention against the effects of chemotherapy.

Recent Advances in Pharmaceutical Approaches of Antimicrobial Agents for Selective Delivery in Various Administration Routes.

Globally, the increase of pathogenic bacteria with antibiotic-resistant characteristics has become a critical challenge in medical treatment. The misuse of conventional antibiotics to treat an infectious disease often results in increased resistance and a scarcity of effective antimicrobials to be used in the future against the organisms. Here, we discuss the rise of antimicrobial resistance (AMR) and the need to combat it through the discovery of new synthetic or naturally occurring antibacterial compounds, as well as insights into the application of various drug delivery approaches delivered via various routes compared to conventional delivery systems. AMR-related infectious diseases are also discussed, as is the efficiency of various delivery systems. Future considerations in developing highly effective antimicrobial delivery devices to address antibiotic resistance are also presented here, especially on the smart delivery system of antibiotics.

Turmeric extract gel and honey in post-cesarean section wound healing: A preliminary study.

Background: Delivery by cesarean section (SC) increases the risk of a surgical site infection (SSI). Therapy from health services and complementary therapy reduce the risk of infection and accelerate the wound-healing process. This study compared wound healing after SC with a turmeric extract gel and original Trigona honey. Methods: Female white rats ( Rattus novergicus) with pre- and post-testing and a control group were included in this experiment, which was conducted in June-July 2022. The test animals were 56 female white rats, 2-4 months old, weighing 150-350 g. The treatment group was divided into three subgroups with application of 50% and 75% turmeric extract gel and Trigona honey. The turmeric was given twice daily, and the honey was divided into two applications of twice a day and once a day. Wounds were assessed using the Reeda Scale. Results: The fastest wound healing occurred in the group given Trigona honey twice daily. Redness, ecchymosis, and edema disappeared in this group on day 9 (score 0), and granulation tissue formed on day 9. The group that was administered 50% and 75% turmeric gel extract and Trigona honey once a day healed by days 12 and 15, respectively; all three of these interventions were better than the control group. Conclusions: Administering Trigona honey twice daily was more effective for accelerating wound healing than the 50% or 75% turmeric extract gel. Original Trigona honey has the potential to be a post-SC wound healing agent.

Investigating forthcoming strategies to tackle deadly superbugs: current status and future vision.

INTRODUCTION: Superbugs are microorganisms that cause disease and have increased resistance to the treatments typically used against infections. Recently, antibiotic resistance development has been more rapid than the pace at which antibiotics are manufactured, leading to refractory infections. Scientists are concerned that a particularly virulent and lethal 'superbug' will one day join the ranks of existing bacteria that cause incurable diseases, resulting in a global health disaster on the scale of the Black Death. AREAS COVERED: This study highlights the current developments in the management of antibiotic-resistant bacteria and recommends strategies for further regulating antibiotic-resistant microorganisms associated with the healthcare system. This review also addresses the origins, prevalence, and pathogenicity of superbugs, and the design of antibacterial against these growing multidrug-resistant organisms from a medical perspective. EXPERT OPINION: It is recommended that antimicrobial resistance should be addressed by limiting human-to-human transmission of resistant strains, lowering the use of broad-spectrum antibiotics, and developing novel antimicrobials. Using the risk-factor domains framework from this study would assure that not only clinical but also community and hospital-specific factors are covered, lowering the chance of confounders. Extensive subjective research is necessary to fully understand the underlying factors and uncover previously unexplored areas.

Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells.

The most common type of skin cancer is melanoma. While significant advances in chemotherapy have occurred in a few instances, only marginal progress has been made in treating metastatic melanoma. Natural medicine has traditionally been used to treat various illnesses, including cancer. The purpose of this study was to identify the active compound in Kaempferia galanga, which could be used to treat melanoma as an anti-metastasis and chemosensitizer agent. The active compound in K. galanga was isolated and identified using chromatography and spectroscopy techniques, and given six compounds. Inhibitory activity on NFκB activation and cell viability was determined using reporter assay methods. Among the isolated compounds, ethyl p-methoxycinnamate (EPMC) demonstrated potent NFκB inhibitory activity against melanoma cell B16F10- NFκB Luc2 with an IC50 of 88.7 µM. Further investigation was conducted by evaluating the anti-metastasis effect of EPMC in vitro by using wound-healing assays, invasion tests, and molecular mechanism assays using Western blotting. NFκB has been implicated in tumorigenesis through the PI3K/Akt/NFκB pathway. The results of this study indicated that EPMCs act as inhibitors of p38 and thereby Akt phosphorylation inhibitors at serine 473, inhibiting NFκB-dependent transcription. Further analysis with paclitaxel demonstrated that the combinations could sensitize to apoptosis in response to well-known chemotherapy agents. Additional studies were conducted using the human melanoma cancer cell line SK-Mel 28. Along with the induction of apoptosis, we observed an increase in p-γH2AX expression (a molecular marker for double strand breaks in DNA damage) in response to treatment with paclitaxel and EPMC. The result showed EPMC to be a potential, viable adjuvant for improving the clinical efficacy of anti-metastatic and cancer chemotherapy.

Current State and Promising Opportunities on Pharmaceutical Approaches in the Treatment of Polymicrobial Diseases.

In recent years, the emergence of newly identified acute and chronic infectious disorders caused by diverse combinations of pathogens, termed polymicrobial diseases, has had catastrophic consequences for humans. Antimicrobial agents have been clinically proven to be effective in the pharmacological treatment of polymicrobial diseases. Unfortunately, an increasing trend in the emergence of multi-drug-resistant pathogens and limited options for delivery of antimicrobial drugs might seriously impact humans' efforts to combat polymicrobial diseases in the coming decades. New antimicrobial agents with novel mechanism(s) of action and new pharmaceutical formulations or delivery systems to target infected sites are urgently required. In this review, we discuss the prospective use of novel antimicrobial compounds isolated from natural products to treat polymicrobial infections, mainly via mechanisms related to inhibition of biofilm formation. Drug-delivery systems developed to deliver antimicrobial compounds to both intracellular and extracellular pathogens are discussed. We further discuss the effectiveness of several biofilm-targeted delivery strategies to eliminate polymicrobial biofilms. At the end, we review the applications and promising opportunities for various drug-delivery systems, when compared to conventional antimicrobial therapy, as a pharmacological means to treat polymicrobial diseases.

Care for perineal tears in vaginal delivery: An update for midwife

Objective: The purpose of this study will be to review several studies regarding the repair or treatment of perineal tears after vaginal delivery. This is expected to be an update for a midwife in daily caring. Methods: Two electronic databases (PubMed and Sciencedirect) were searched to locate relevant literature about perineal tears/wound/laceration/trauma that is published in 2016–2021. 124 Pubmed articles and 452 ScienceDirect articles filtered successfully. The articles that have been obtained will be evaluated based on the inclusion criteria in this study. We summarize place and date, objective, design, samples, the measurement used, and research results. Results: 9 articles were found that matched the inclusion criteria. Three articles examined the effect of the type of suture on perineal pain, and another 6 discussed therapy to reduce the adverse effects of perineal tears. The therapies used are far-infrared radiation therapy, capacitive-resistive radiofrequency therapy, pelvic floor muscle training in early postpartum, cold therapy, and treatment with TheresienOl (natural oil). Conclusion: Sutures and technique/suturing second-degree perineal tears or a postpartum episiotomy can affect perineal pain. Cold gel pad therapy and treatment with natural oil on perineal wounds can affect perineal pain and wound healing. (AU)

Potential Roles of Kleinhovia hospita L. Leaf Extract in Reducing Doxorubicin Acute Hepatic, Cardiac and Renal Toxicities in Rats.

BACKGROUND: Doxorubicin (DOX) is a potent chemotherapy agent; however, its use may lead to cardiac, hepatic, and renal dysfunction. Kleinhovia hospita L extract contains antioxidant compounds that have been shown to reduce chemical-induced hepatotoxicity. OBJECTIVES: This study aimed to examine the protective effects of Kleinhovia sp. extract to reduce DOX acute toxicities. MATERIALS AND METHODS: Thirty male rats were assigned to the following groups: Group I as controls, Group II was given DOX i.p. injection (25 mg/kg); Groups III, IV, and V were treated with Kleinhovia sp. extract 100, 250, and 500 mg/kg orally for 5 days, respectively, prior to DOX i.p. injection. After 24 h, blood and organs were analyzed for biomarker levels and histopathological changes. RESULTS: DOX treatment in Group II significantly increased creatine kinase-MB (CK-MB), aspartate transaminase (AST), alanine transaminase (ALT), and urea levels compared to controls. Kleinhovia sp. extract at any given dose significantly improved ALT and AST; yet, CK-MB levels only reduced with 250 mg/kg dose (Group IV). Urea and creatinine levels in Kleinhovia sp. groups were also lower compared to DOX-treated rats, but it was not significant. Histopathological analysis showed improved liver, heart, and renal tissue structures in Kleinhovia sp-treated rats, especially at higher doses. CONCLUSION: Kleinhovia sp. extract at any dose given protected the rats from liver toxicity, but only at dose 250 mg/kg reduced cardiac toxicity. Although renal biomarkers were insignificantly lower, renal architecture was improved with Kleinhovia sp. treatment. SUMMARY: Doxorubicin (25 mg/kg) i.p injection led to elevated ALT, AST, CK-MB and urea levels in rats.At the given dose, doxorubicin induced pathological changes in cardiac, liver and renal tissues.Pretreatment with Kleinhovia sp. extract prior to doxorubicin injection significantly reduced the elevation of ALT, AST and CK-MB, especially at the dose of 250 mg/kg.Improvement in histological structures of cardiac, liver and renal tissues was shown in Kleinhovia sp. (250 mg/kg) treated rats, indicating a protective effect of the extract on doxorubicin acute toxicity. Abbreviations Used: DOX: Doxorubicin; CK-MB: creatine kinase-MB, AST: Aspartate transaminase; ALT: Alanine transaminase.