Recurrent aphthous stomatitis (RAS) is a disease marked by painful oral lesions on the buccal and labial mucosa or tongue. Drug delivery systems (DDS) for RAS include topical forms that manage wound healing, cover the ulcer, and relieve the associated pain. DDS targeting the oral mucosa face a major challenge, especially the short residence times in the mouth due to the effect of “saliva wash-out”, which continually removes the drug. The objective of this review is to study the development of preparation forms and delivery systems of various types and preparations that have been used for RAS management from 1965 until February 2020. There are 20 types of DDS for RAS which were discussed in 62 articles. The preparations were classified into 4 preparation forms: liquid, semi-solid, solid, and miscellaneous. In addition, the ultimate DDS for RAS preparations is the semi-solid forms (41.94%), which include 5 types of DDS are gel, paste, patch, cream, and ointment. This preparation was developed into new preparation form (11.29%), such as adhesive alginates, dentifrice, OraDisc, membranes, bioresorbable plates, pellicles, and gelosomes. Generally, the mucosal drug delivery system is the method of choice in RAS treatment because the ulcer is commonly located in the oral mucosa. In conclusion, these preparations are designed to improve drug delivery and drug activity for the treatment of RAS ulcers. Moreover, almost all of these DDS are topical preparations that use various types of mucoadhesive polymers to increase both residence time in the oral mucosa and pain relief in RAS treatment.
α-Mangostin (α-M), one of the active compounds in Garcinia mangostana peel, has been effectively used in wound healing. However, its poor solubility in aqueous solution causes low bioavailability for skin ulcers, hindering its application in wound healing. The aim of this study was to improve the solubility of α-M through complex formation with 2-hydroxypropyl-β-cyclodextrin (α-M/HP-β-CD CX) and to evaluate the healing activity of the complex. The α-M/HP-β-CD CX was incorporated in a sodium carboxymethylcellulose hydrogel (α-M/HP-β-CD CX HG), and the in vivo healing activity was examined in mice. Evaluation of α-M/HP-β-CD CX HG, including organoleptic evaluation, homogeneity, pH, spreadability, swelling ratio, consistency, scanning electron microscopy (SEM), and in vitro drug release, was carried out. The complex formation of α-M/HP-β-CD CX was confirmed by FTIR and PXRD analysis. The solubility of the α-M/HP-β-CD CX in water linearly increased about 11.7-fold compared to α-M alone, and by 3.5-fold compared to the α-M/HP-β-CD physical mixture (α-M/HP-β-CD CX PM). The α-M/HP-β-CD CX HG was homogenous, the pH was found to be in the neutral range, the spread area was 5 cm, and the consistency was stable until 14 days. SEM analysis showed that α-M/HP-β-CD CX HG surged due to the porous structure of the HG. In addition, in vitro release of α-M from α-M/HP-β-CD CX HG was considerably increased compared to α-M/HP-β-CD PM HG and α-M HG. Notably, in vivo evaluation in mice showed that α-M/HP-β-CD CX HG significantly accelerated the wound healing ability compared to other HGs. Thus, α-M/HP-β-CD CX HG has potential as a new formulation of α-M for wound healing therapy.
α-Mangostin (a xanthone derivative found in the pericarp of Garcinia mangostana L.) and propolis extract (which is rich in flavonoids and phenols) are known for their antioxidant properties, making them potential supplements for the treatment of oxidative stress-related conditions. However, these two potential substances have the same primary drawback, which is low solubility in water. The low water solubility of α-mangostin and propolis can be overcome by utilizing nanotechnology approaches. In this study, a propolis-based nanostructured lipid carrier (NLC) system was formulated to enhance the delivery of α-mangostin. The aim of this study was to characterize the formulation and investigate its influence on the antioxidant activity of α-mangostin. The results showed that both unloaded propolis-based NLC (NLC-P) and α-mangostin-loaded propolis-based NLC (NLC-P-α-M) had nanoscale particle sizes (72.7 ± 1.082 nm and 80.3 ± 1.015 nm, respectively), neutral surface zeta potential (ranging between +10 mV and −10 mV), and good particle size distribution (indicated by a polydispersity index of <0.3). The NLC-P-α-M exhibited good entrapment efficiency of 87.972 ± 0.246%. Dissolution testing indicated a ~13-fold increase in the solubility of α-mangostin compared to α-mangostin powder alone. The incorporation into the propolis-based NLC system correlated well with the enhanced antioxidant activity of α-mangostin (p < 0.01) compared to NLC-P and α-mangostin alone. Therefore, the modification of the delivery system by incorporating α-mangostin into the propolis-based NLC overcomes the physicochemical challenges of α-mangostin while enhancing its antioxidant effectiveness.
Recurrent aphthous stomatitis (RAS) is a prevalent clinical disorder that causes mouth ulcers. Furthermore, corticosteroid treatment has been widely utilized for RAS therapy; however, it has side effects on the oral mucosa that limit its application. This study aimed to develop a novel RAS therapy with the natural ingredient α-mangostin, delivered by alginate and chitosan polymers-based hydrogel film (α-M Alg/Chi-HF). To prepare α-M Alg/Chi-HF, the solvent evaporation and casting methods were used, then characterized by using SEM, FTIR, and XRD. Based on the characterization studies, the α-M in α-M/EtOH Alg/Chi-HF with ethanol (EtOH) was found to be more homogenous compared to α-M in Alg/Chi-HF with distilled water (H2O) as a casting solvent. The in vitro viability study using NIH3T3 cells showed 100% viability of α-M Alg/Chi-HF (EtOH) and Alg/Chi-HF after 24 h incubation, indicating well tolerability of these hydrogel films. Interestingly, the in vivo studies using male white rats (Rattus norvegicus Berkenhout) proved that α-M/EtOH Alg/Chi-HF with a recovery of 81.47 ± 0.09% in seven days significantly more effective RAS therapy compared to control. These results suggest that α-M/EtOH Alg/Chi-HF has the potential as an alternative for RAS therapy.
α-Mangostin (α-M) has various biological activities, such as anti-cancer, antibacterial, anti-fungal, anti-tyrosin, anti-tuberculosis, anti-inflammatory, and antioxidant. However, it has very low solubility in water. The formulation of this compound requires high amounts of solubilizers, which limits its clinical application. In addition, its low solubility in water is a barrier to the distribution of this drug, thus affecting its potency. Cyclodextrin (CD) is widely used as a solubility enhancer of poorly soluble drugs. This study aimed to increase the solubility of α-M in water through complex formation with CD. The complex of α-Mangostin and γ-Cyclodextrin (α-M/γ-CD CX) was prepared by the solubilization method, resulting in a solubility improvement of α-M in water. Characterization of α-M/γ-CD CX by using FTIR-Spectrometry, XRD, H-, C-, and HMBC-NMR showed that α-M was able to form an inclusion complex with γ-CD. The complex yielded an entrapment efficiency of 84.25 and the thermodynamic study showed that the α-M/γ-CD CX was formed spontaneously, based on the negative values of Gibbs energy and ΔH. Interestingly, the solubility of α-M/γ-CD CX significantly increased by 31.74-fold compared with α-M. These results suggest that α-M/γ-CD CX has the potential in the formulation of water-based preparation for clinical applications.
Most recently discovered active pharmaceutical molecules and market-approved medicines are poorly soluble in water, resulting in limited drug bioavailability and therapeutic effectiveness. The application of coformers in a multicomponent crystal method is one possible strategy to modulate a drug’s solubility. A multicomponent crystal is a solid phase formed when several molecules of different substances crystallize in a crystal lattice with a certain stoichiometric ratio. The goal of this review paper is to comprehensively describe the application of coformers in the formation of multicomponent crystals as solutions for pharmaceutically active ingredients with limited solubility. Owing to their benefits including improved physicochemical profile of pharmaceutically active ingredients, multicomponent crystal methods are predicted to become increasingly prevalent in the development of active drug ingredients in the future
This review article aimed to study chitosan as a material based in wound dressing preparation. The method in this review is the approximation method. The articles were obtained from national and international journals such as Scopus, PubMed, and Google Scholar by using the keywords "Chitosan", "Wound Healing", and "Biomedical Application". The inclusion criteria of the article are: national and international journals and books contains chitosan as, published in the last ten years, and not review article. The final articles used in this review are 29 articles that studying the use of chitosan as wound dressing material. The combination of chitosan with some polymer, ion and other materials resulting the chitosan-based materials namely nanofibrous membranes, composites sponge, polyelectrolyte complex, and composites, that used in topical preparation such as membranes, fibers, sponge, film, and gel. Thus, the modified of chitosan wound healing preparation resulting in the improve of healing activity of each preparation from. This review summarizes chitosan application in wound healing. Several studies were proposed the porous structure of chitosan-based materials lead the improvement of healing activity.
Madu merupakan substrat yang telah banyak digunakan oleh masyarakat Indonesia untuk pengobatan, salah satunya digunakan untuk mengobati jerawat. Madu memiliki daya hambat antimikroba, kemampuan antimikroba pun terdapat pada bahan alam lain salah satunya Bawang Putih Tunggal (Allium sativum L.). Trend masyarakat terhadap kedua bahan alam tersebut salah satunya dengan mengkombinasikan Madu dan Bawang Putih Tunggal (Allium sativum L.) menggunakan metode perendaman Bawang Putih Tunggal (Allium sativum L.) dalam Madu. Penelitian ini bertujuan untuk mengetahui daya hambat bakteri madu hasil fermentasi terhadap bakteri Propionibacterium acnes. Pengujian daya hambat menggunakan metode difusi kertas cakram dengan sampel Madu hasil fermentasi dengan Bawang Putih tunggal (Allium sativum L.) terhadap lama waktu fermentasi Madu, kontrol positif (Klindamisin 300 mg), dan kontrol negatif (aquadest). Sampel Madu dan Bawang Putih Tunggal (Allium sativum L.) di fermentasi menggunakan lama waktu fermentasi pada pekan ke 1,2,3 dan 4. Hasil penelitian menunjukkan bahwa lama waktu fermentasi madu dapat meningkatkan daya hambat pertumbuhan bakteri Propionibacterium acnes dengan adanya zona bening disekitar kertas cakram. Diameter hambat fermentasi madu pada pekan 1,2,3 dan 4 yaitu 0,416 mm, 0,65 mm, 0,775 mm dan 1,8 mm. Dapat disimpulkan bahwa semakin lama waktu fermentasi Madu dan Bawang Putih Tunggal (Allium sativum L.) akan mengalami kenaikan diameter pada zona bening daya hambat nya diketahui pada pekan ke empat memiliki daya hambat paling besar 1,8 mm.
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