The Formulation and Characterization of Wound Dressing Releasing S-Nitrosoglutathione from Polyvinyl Alcohol/Borax Reinforced Carboxymethyl Chitosan Self-Healing Hydrogel.

Self-healing hydrogels often lack mechanical properties, limiting their wound-dressing applications. This study introduced S-Nitrosoglutathione (GSNO) to self-healing hydrogel-based wound dressings. Self-healing hydrogel mechanical properties were improved via polymer blends. Applying this hydrogel to the wound site allows it to self-heal and reattach after mechanical damage. This work evaluated polyvinyl alcohol (PVA)-based self-healing hydrogels with borax as a crosslinking agent and carboxymethyl chitosan as a mechanical property enhancer. Three formulations (F1, F4, and F7) developed self-healing hydrogels. These formulations had borax concentrations of 0.8%, 1.2%, and 1.6%. An FTIR study shows that borate ester crosslinking and hydrogen bonding between polymers generate a self-healing hydrogel. F4 has a highly uniform and regular pore structure, as shown by the scanning electron microscope image. F1 exhibited faster self-healing, taking 13.95 ± 1.45 min compared to other formulations. All preparations had pH values close to neutrality, making them suitable wound dressings. Formula F7 has a high drug content (97.34 ± 1.21%). Good mechanical qualities included high tensile stress-strain intensity and Young's modulus. After 28 h of storage at -20 °C, 5 °C, and 25 °C, the self-healing hydrogel's drug content dropped significantly. The Korsmeyer-Peppas release model showed that the release profile of GSNO followed Fickian diffusion. Thus, varying the concentration of crosslinking agent and adding a polymer affects self-healing hydrogels' physicochemical properties.

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.

Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan.

Telmisartan (TEL) is a promising antihypertensive agent among other angiotensin receptor blockers. However, its oral application is limited by its poor water solubility. This study presents the successful utilization of biomaterial-based hydrogel-forming microneedles integrated with a direct compressed tablet reservoir (HFMN-DCT) for the transdermal delivery of telmisartan in the treatment of hypertension. The combination of PVP, PVA, and tartaric acid was used in the HFMN formulation. A range of cross-linking temperatures and times were employed to optimize the characteristics of the HFMN. The HFMN exhibited excellent swelling capacity, mechanical strength, and insertion properties. Additionally, the poorly soluble characteristic of TEL was improved by the inclusion complex formulation with ß-cyclodextrin (ßCD). Phase solubility analysis showed an Ap-type diagram, indicating a higher-order complex between TEL and ßCD, with respect to ßCD. A ratio of TEL:ßCD of 1:4 mM demonstrates the highest solubility enhancement of TEL. The inclusion complex formation was confirmed by FTIR, XRD, DSC, and molecular docking studies. A significantly higher release of TEL (up to 20-fold) from the inclusion complex was observed in the in vitro release study. Subsequently, a DCT reservoir was developed using various concentrations of sodium starch glycolate. Essentially, both the HFMN and DCT reservoir exhibit hemocompatibility and did not induce any skin irritation. The optimized combination of the HFMN-DCT reservoir showed an ex vivo permeation profile of 83.275 ± 2.405%. Notably, the proposed system showed superior pharmacokinetic profiles in the in vivo investigation using male Wistar rats. Overall, this study highlights the potential of HFMN-DCT reservoir systems as a versatile platform for transdermal drug delivery applications.

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.

Enhanced skin localization of metronidazole using solid lipid microparticles incorporated into polymeric hydrogels for potential improved of rosacea treatment: An ex vivo proof of concept investigation.

Metronidazole (MNZ) is a nitroimidazole derivative antibiotic that has been generally used in the treatment of rosacea. However, it has low molecular weight and lipophilicity, limiting the effectiveness of MNZ in the topical treatment of rosacea. This study reports an MNZ-loaded solid lipid microparticle (SLM) gel formulation with sustained drug release effects required in the treatment of rosacea. SLM was formulated using the double emulsification method with five different concentrations of glyceryl monostearate (GMS) as a solid lipid used to encapsulate MNZ. All the MNZ-loaded SLM formulas were extensively characterized by various analytical tools. After optimized MNZ-loaded SLM formulation was obtained, then formulated into gel preparation. To obtain a gel formula with good physical characteristics and drug release in the development of topical therapy, the SLM-loaded gel was further evaluated, covering various parameters such as pH, viscosity, rheology, spreadability, extrudability, skin occlusivity, gel strength, permeation and retention ex vivo, as well as hemolysis tests and antioxidant activity. The evaluation results showed that the SLM formulations had desired properties with optimum encapsulation efficiency. Moreover, the gels prepared from carbomer possessed desired characteristics and were found to be hemocompatible. In addition, the gel formula with a carbomer concentration of 1.25 % can provide better drug release with the highest MNZ retention after 24 h of 2.35 ± 0.05 mg. Notably, the formulation of MNZ into SLM and hydrogel did not affect the antioxidant activity. Thus, it can provide continuous drug release, which could potentially be useful in increasing efficacy in rosacea therapy. The results obtained also showed a significant difference (p < 0.05) compared to the control formula and other formulas. Therefore, this study has proven a new approach to developing drug delivery systems for rosacea treatment.

Potency of complemeter therapy to the healing process of perineal wound; turmeric (Curcuma longa Linn) Infusa.

OBJECTIVE: The purpose of this study was to assess the effectiveness of yellow turmeric-infusa of 5% and 10% on the healing process of perineal wound grade II. METHOD: The method used in this study is quasi-experiment with Pretest-Posttest Control Group design. The sampling technique is Exhaustive Sampling according to inclusion criteria. In this research consisted of three experimental groups with two intervention groups and one control group, with the number of subjects group was 15 people. Turmeric infusa is used daily by washing in the perineal wound area two times a day for 5 days postpartum. Monitoring of grade II perineal wound was performed three times, days 1, 5, and 7 postpartum using REEDA scale assessment. Data analysis used Kruskal-Wallis and Chi-Square tests. RESULTS: The results showed that on the 5th and 7th postpartum days, there were differences in redness, edema, and approximation of wounds in each group (p<0.05) while the other REEDA parameters were not significantly different. There is also a difference in the time of perineal wound healing in each group, and it can be seen from the decrease and the total REEDA score. Turmeric infusa group 5% experienced healing on the 5th day postpartum, turmeric infusa 10% recovered on the 7th day postpartum, and the control group recovered more than 7 days. CONCLUSION: Giving turmeric was proven to eliminate redness, edema, accelerate the closure, and perineal wound healing time, as seen from the p-value (p<0.05). However, turmeric infusa of 5% and 10% showed better effectiveness than turmeric infusa of 5%.

Characterization and Biological Evaluation of Solid Dispersed Nanoparticles of Synthetic Epoksilignan Targeting Pancreatic Cancer Cell as an Anticancer Agent.

MMEO (3'-methoxy-3',4″(methylenedioxy)-2,5-epoksilignan-4'ol-6-on) is a derivative of DMEO (3'-methoxy-3″,4″(methylenedioxy)-2,5-epoksilignan-4',6-diol) synthesized through demethylation using dimethylsulfoxide-acetic anhydride reagent. MMEO inhibits Hedgehog signaling at a concentration of 4.1 µM. The current study aimed to formulate MMEO as solid dispersed nanoparticles and determine their physicochemical properties and inhibitory activities. XRD (X-ray diffraction) analysis showed that the crystalline particles of the pure compound MMEO was smaller than MMEO nanoparticles. Image J software showed that at concentrations of 25 mg/mL and 50 mg/mL, the average nanoparticle sizes were 852.26 nm and 178.65 nm, respectively. Therefore, the MMEO solid dispersion system with the PEG 4000 polymer increases the solubility of MMEO. The higher the concentration of PEG 4000 the greater the solubility of MMEO. Treating pancreatic cancer cell lines with MMEO silenced the smoothened function by downregulating mRNA Ptch expression. This study suggests that MMEO may inhibit pancreatic cancer disease.

Potency of complemeter therapy to the healing process of perineal wound; turmeric (Curcuma longa Linn) Infusa

Objective: The purpose of this study was to assess the effectiveness of yellow turmeric-infusa of 5% and 10% on the healing process of perineal wound grade II. Method: The method used in this study is quasi-experiment with Pretest–Posttest Control Group design. The sampling technique is Exhaustive Sampling according to inclusion criteria. In this research consisted of three experimental groups with two intervention groups and one control group, with the number of subjects group was 15 people. Turmeric infusa is used daily by washing in the perineal wound area two times a day for 5 days postpartum. Monitoring of grade II perineal wound was performed three times, days 1, 5, and 7 postpartum using REEDA scale assessment. Data analysis used Kruskal–Wallis and Chi-Square tests. Results: The results showed that on the 5th and 7th postpartum days, there were differences in redness, edema, and approximation of wounds in each group (p < 0.05) while the other REEDA parameters were not significantly different. There is also a difference in the time of perineal wound healing in each group, and it can be seen from the decrease and the total REEDA score. Turmeric infusa group 5% experienced healing on the 5th day postpartum, turmeric infusa 10% recovered on the 7th day postpartum, and the control group recovered more than 7 days. Conclusion: Giving turmeric was proven to eliminate redness, edema, accelerate the closure, and perineal wound healing time, as seen from the p-value (p < 0.05). However, turmeric infusa of 5% and 10% showed better effectiveness than turmeric infusa of 5%. (AU)

Phytosomal nanocarriers as platforms for improved delivery of natural antioxidant and photoprotective compounds in propolis: An approach for enhanced both dissolution behaviour in biorelevant media and skin retention profiles.

Propolis has been reported to possess rich content of antioxidant compounds and may provide health benefits through oxidative stress reduction. Presently, the formulation activities used to enhance the drug delivery have been hampered due to inherently low aqueous solubility and poor transdermal permeation of the bioactive phenols and flavonoids. Here, we show, the formulation of propolis extract (PE) into phytosome delivery systems. The optimum antioxidant activity was attained through extraction process using 75% v/v ethanol. The phytosome was prepared using thin-layer hydration technique with l-α-Phosphatidylcholine as a phospholipid. Fourier transform infrared (FTIR) was used to investigate the occurrence of molecular interactions between formulation components. This innovative approach could encapsulate >40% of bioactive compounds in PE, namely caffeic acid, quercetin, and kaempferol. FTIR spectroscopy indicated new hydrogen bond formation, supporting successful phytosome formulation. The phytosomes enhanced the dissolution up to 4-folds of bioactive compounds in bio-mimicked release media, as well as improved penetrability and skin retention up to 6-folds of the three main compounds of propolis, when compared to non-encapsulated PE formulation. Importantly, the hydrogel containing phytosome showed a potential for UVA and UVB radiation absorption, indicated by the SPF values of higher than 15. To conclude, this work shows promising novel delivery approaches for PE in the treatment of organ injured stress oxidative and skin aging.

Characterization and stability evaluation of nanoencapsulated epoxylignans.

3',6-dimethoxy-3'',4''-(methylenedioxy)-2,5-epoxylignan-4'-ol (DMEO), an epoxylignan isolated from Piper nigrum, has currently captured attention for its potential antitumor effect. However, low stability is limiting its therapeutic application. The application of nanocapsulation would be the main strategy for overcoming this problem. DMEO-loaded nanocapsules were prepared by an emulsion-diffusion method using Eudragit RL 100 (at concentrations of 1, 1.5 and 2%) and polyvinyl alcohol. As the polymer content increased, the encapsulation efficiency and mean particle size also increased. After 6 months of storage at 25°C (0% RH), no crystalline peaks were observed in the diffraction patterns of all nanocapsules, thereby suggested that the physical stability of nanoencapsulated DMEO was not affected by the concentration ratio of the polymer-stabilizer combinations.

Addressing non-communicable diseases in Malaysia: an integrative process of systems and community.

The prevalence of non-communicable diseases (NCDs) and NCD risk factors in Malaysia have risen substantially in the last two decades. The Malaysian Ministry of Health responded by implementing, "The National Strategic Plan for Non-Communicable Diseases (NSP-NCD) 2010-2014", and the "NCD Prevention 1Malaysia" (NCDP-1M) programme. This paper outlines the primary health system context in which the NCDP-1M is framed. We also discuss the role of community in facilitating the integration of this programme, and outline some of the key challenges in addressing the sustainability of the plan over the next few years. The paper thus provides an analysis of an integration of a programme that involved a multi-sectoral approach with the view to contributing to a broader discourse on the development of responsive health systems.

Association between pregnancy induced hypertension and low birth weight; a population based case-control study.

The purpose of this study was to investigate the association between pregnancy-induced hypertension and low birth weight. A population-based case control study was conducted. Antenatal mothers who attended the government health centers in the district of Kuala Muda, Kedah, Malaysia from June 2003 to May 2004 were recruited. Cases were 312 mothers who delivered low birth weight babies, and controls were 312 mothers who delivered normal birth weight babies. Face-to-face interviews using a structured questionnaire and a review of medical records were carried out. After controlling for important confounders such as gestational age at delivery, maternal age, ethnicity, education, parity, and previous history of abortion, pregnancy-induced hypertension was found to be an independent risk factor (adjusted odds ratio = 5.06; 95% confidence interval: 2.63, 9.71) for low birth weight. There was a significant association of pregnancy-induced hypertension with low birth weight. Women who delivered low birth weight babies were 5 times more likely to have had pregnancy-induced hypertension.