Development of dissolving microneedles loaded with fucoidan for enhanced anti-aging activity: An in vivo study in mice animal model.

Skin aging occurs naturally as essential skin components gradually decline, leading to issues such as fine lines, wrinkles, and pigmentation. Fucoidan, a natural bioactive compound, holds potential for addressing these age-related concerns. However, its hydrophilic nature and substantial molecular weight hinder its absorption into the skin. In this study, we utilized polyvinyl pyrrolidone K30 (PVP) and polyvinyl alcohol (PVA) as polymers to fabricate dissolving microneedles loaded with fucoidan (DMN-F). The DMN-F formulations were examined for physical characteristics, stability, permeability, toxicity, and efficacy in animal models. These formulations exhibited consistent polymer blends with a conical structure and uniform cone-shaped design. Microneedle structure and penetration capability gradually decreased with increasing fucoidan concentration, with storage recommended at approximately 33 % relative humidity (RH). Ex vivo studies showed that DMN-F efficiently delivered up to 95.03 ±â€¯2.36 % of the total fucoidan concentration into the skin. In vivo investigations revealed that DMN-F effectively reduced wrinkles, improved skin elasticity, maintained moisture levels, and increased epidermal thickness. Histological images provided additional evidence of DMN-F's positive effects on these aging parameters. The results confirm that the DMN-F formulation effectively delivers fucoidan into the skin, allowing it to treat and mitigate signs of aging.

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.

Development of probiotic loaded multilayer microcapsules incorporated into dissolving microneedles for potential improvement treatment of vulvovaginal candidiasis: A proof of concept study.

Vulvovaginal candidiasis (VVC) is a vaginal infection caused by abnormal growth of Candida sp., especially Candida albicans, in the vaginal mucosa. A shift in vaginal microbiota is prominent in VVC. The presence of Lactobacillus plays a vital role in maintaining vaginal health. However, several studies have reported resistance of Candida sp. against azoles drugs, which is recommended as VVC treatment. The use of L. plantarum as a probiotic would be an alternative to treat VVC. In order to exert their therapeutic activity, the probiotics needed to remain viable. Multilayer double emulsion was formulated to obtain L. plantarum loaded microcapsules (MCs), thus improving its viability. Furthermore, a vaginal drug delivery system using dissolving microneedles (DMNs) for VVC treatment was developed for the first time. These DMNs showed sufficient mechanical and insertion properties, dissolved rapidly upon insertion, facilitating probiotic release. All formulations proved non-irritating, non-toxic, and safe to apply on the vaginal mucosa. Essentially, the DMNs could inhibit the growth of Candida albicans up to 3-fold than hydrogel and patch dosage forms in ex vivo infection model. Therefore, this study successfully developed the formulation of L. plantarum-loaded MCs with multilayer double emulsion and its combination in DMNs for vaginal delivery to treat VVC.

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.

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.