ABSTRACT
Ketoprofen is an anti-inflammatory agent that may cause gastric irritation if administered orally. Dissolving microneedles (DMN) can be a promising strategy to overcome this issue. However, ketoprofen has a low solubility; therefore, it is essential to enhance its solubility using certain methods, namely nanosuspension (NS) and co-grinding (CG). This research aimed to formulate DMN containing ketoprofen-loaded NS and CG. Ketoprofen NS was formulated with poly(vinyl alcohol) (PVA) at concentrations of 0.5%, 1%, and 2%. CG was prepared by grinding ketoprofen with PVA or poly(vinyl pyrrolidone) (PVP) at different drug-polymer ratios. The manufactured ketoprofen-loaded NS and CG were evaluated in terms of their dissolution profile. The most promising formulation from each system was then formulated into microneedles (MNs). The fabricated MNs were assessed in terms of their physical and chemical properties. An in vitro permeation study using Franz diffusion cells was also carried out. The most promising MN-NS and MN-CG formulations were F4-MN-NS (PVA 5%-PVP 10%), F5-MN-NS (PVA 5%-PVP 15%), F8-MN-CG (PVA 5%-PVP 15%), and F11-MN-CG (PVA 7.5%-PVP 15%), respectively. The cumulative amounts of drug permeated after 24 h for F5-MN-NS and F11-MN-CG were 3.88 ± 0.46 µg and 8.73 ± 1.40 µg, respectively. In conclusion, the combination of DMN with nanosuspension or a co-grinding system may be a promising strategy for delivering ketoprofen transdermally.
ABSTRACT
BACKGROUND: Macassar kernels (Rhus javanica L.) has potential as an antiaging agent as it has antielastase activity, especially its stem extract which has best percent inhibition compared to its leaves and fruit extract. Moreover, the antiaging agent can be commonly used in the form of gel for topical applications. Hence, formulation of HEC-based topical gel from the stem extract of Macassar kernels was conducted. This study aims to determine the antielastase activity of the stem extract of Macassar kernels and evaluate the skin elasticity of its topical gel formulation by conducting dermatological safety and skin antiaging efficacy test. METHODS: The stem extract was in vitro tested for antielastase activity using a microplate reader. Then, a formulation of a topical gel containing Rhus javanica stem extract was made. Five stages of quality control, which consisted of an organoleptic test, homogeneity test, pH measurement, viscosity measurement, and physicochemical stability test, were conducted to ensure the quality of topical gel formulation. Last, clinical studies were conducted to evaluate the dermatological safety and antiaging efficacy of gel preparation containing stem extract of Rhus javanica. Results. The stem extract provided antielastase activity (IC50 = 245.68 µg/mL), and its polyphenol was valued at 23.28 ± 1.52 mg GAE/g). The gel containing 10% stem extract had better stability than the gel containing 5% stem extract. The dermatology safety test and efficacy test results indicated that the topical gel containing 10% Rhus javanica stem extract did not cause any skin irritation and significantly improved skin elasticity (p < 0.05). In the treatment group, the moisture parameter was significantly changed on day 14 (p < 0.0001), day 21 (p < 0.0001), and day 29 (p < 0.0001). The elasticity parameter was also changed significantly on day 14 (p=0.0485), day 21 (p=0.0537), and day 29 (p=0.0002). CONCLUSION: The stem extract of Rhus javanica has potential antielastase activity. The topical gel containing Rhus javanica stem extract also has potential antielastase activity by increasing the skin moisture and enhancing skin elasticity.
ABSTRACT
Azelaic acid is an antiacne drug by inhibiting thioredoxin reductase enzyme of Propionibacterium acnes (P. acnes) that affects the inhibition of bacterial DNA synthesis which occurs in the cytoplasm. Azelaic acid must penetrate through the stratum corneum to the sebaceous tissue and into cytoplasm by passing through thick peptidoglycan of P. acnes. Thus, it is necessary to increase the penetration of azelaic acid that formulated based ethosome. This study using thin-layer hydration method forms an ethosomal suspension with variations of concentration ethanol (30%, 35%, and 40%). Antibacterial activity was conducted using broth dilution method to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibacterial activity of azelaic acid ethosome cream based was compared with the marketed cream (Zelface® cream). Azelaic acid ethosome with 35% ethanol has given best result with entrapment efficiency of 94.48% ± 0.14%. Antibacterial activity to P. acnes showed that azelaic acid ethosome-based cream was given better activity than marketed cream (Zelface® cream). The value of MIC and MBC of azelaic acid ethosome-based cream was 250 µg/ml while the marketed cream (Zelface® cream) was shown MIC of 250 µg/ml and MBC of 500 µg/ml. This study proved that the azelaic acid ethosome-based cream has better antibacterial activity.
ABSTRACT
Prior study has shown that Ageratum conyzoides L. extract that containing quercetin has been proved to prevent inflammation and proteoglycan degradation by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase (MMP-9) expression. Target of osteoarthritis (OA) treatment was in the synovial joint that requiring a drug delivery system. The aim of this study was to prove the efficacy of quercetin-loaded lecithin-chitosan nanoparticles on the OA model rats by observed its effect on interleukin (IL-1) ß, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) expressions. In this study, 70 white male Sprague Dawley rats were divided into 14 groups, 7 groups each for destabilization of medial meniscus (DMM) and monoiodoacetate (MIA)-induced OA. After 28 days from induction, SHAM and negative group received gel base topically; positive group received sodium diclofenac gel; three-dose group received each 0.84, 1.68, 3.36 mg/g quercetin-loaded nanoparticles gel; and A. conyzoides L. group received A. conyzoides L. extract gel. Each group gets treatment until day 70, and then, blood sample was collected for serum analysis; knee joint was isolated and subjected to histology samples treatment. Quercetin-loaded nanoparticle gel dose 1 (0.84 mg/g gel), dose 2 (1.68 mg/g gel), dose 3 (3.36 mg/g), and A. conyzoides L. extract gel could decreased the level of IL-1 ß, MMP-9, MMP-13, ADAMTS-5, and increasing color intensity significantly on histopathological observations on DMM and MIA-induced OA.
