Uji Disolusi Terbanding Zat Karbamazepin dalam Bentuk Sediaan Tablet

Dalam penelitian ini telah dilakukan uji ekivalensi produk tablet karbamazepin secara in vitro dengan menggunakan uji disolusi terbanding. Uji dilakukan terhadap produk inovator, produk bermerek I, dan produk bermerek II menggunakan 3 medium uji yaitu medium pH 1,2; pH 4,5; dan pH 6,8 dengan pengambilan sampel pada menit ke-10, 15, 30, 45, dan 60. Penetapan kadar dilakukan menggunakan metode spektrofotometri UV pada panjang gelombang 285 nm. Hasil uji disolusi terbanding dianalisis menggunakan faktor kemiripan (f2). Dari hasil uji disolusi terbanding, kedua produk uji tidak ekivalen terhadap produk inovator

Formulasi dan Karakterisasi Sediaan Mukoadhesif Ekstrak Etanol Centella asiatica (L.) urb.

Tujuan penelitian ini adalah untuk mengembangkan dan mengevaluasi sediaanmikrosfer mukoadhesif dari ekstrak etanol Centella asiatica yang diketahui memiliki aktivitas antitukak lambung. Simplisia C. asiatica diekstraksi dengan metode refluks menggunakan etanol. Formulasi mikrosfer dilakukan dengan metode gelasi ionotropik menggunakan natrium alginat yang diinkorporasi dengan ekstrak etanol kental serta kitosan dalam larutan kalsium klorida. Variasi dilakukan terhadap konsentrasi natrium alginat, rasio bobot ekstrak dan natrium alginat, konsentrasi kitosan, dan konsentrasi kalsium klorida. Evaluasi meliputi ukuran dan distribusinya, karakteristik permukaan, efisiensi penjeratan, profil kapasitas mengembang, serta uji mukoadhesi in vitro. Formula optimum diperoleh dengan komposisi 3% natrium alginat, rasio ekstrak-natrium alginat 1:2, 0,5% kitosan, dan 0,5 M kalsium klorida. Mikrosfer yang dihasilkan memiliki distribusi ukuran terbanyak antara 630-710 μm, efisiensi penjeratan 25,48 ± 1,88%, pertambahan bobot pada uji kapasitas mengembang 40,76 ± 1,51% (t=15 menit), dan kekuatan adhesi 78,67 ± 2,89%

PENGEMBANGAN FORMULA NANOSTRUCTURED LIPID CARRIER (NLC) SEBAGAI PEMBAWA MINYAK ATSIRI MELATI (Jasminum officinale L.) SERTA POTENSI AKTIVITAS ANTIOKSIDAN

Potensi penggunaan minyak atsiri sebagai bahan baku obat dan kosmetik sangat menjanjikan, salah satunya minyak atsiri melati (Jasminum officinale L.) yang telah dilaporkan memiliki berbagai aktivitas farmakologi. Namun dikarenakan karakteristiknya yang mudah menguap, rentan terdegradasi, dan kelarutannya yang rendah dalam air menyebabkan keterbatasan dalam penggunaannya. Selain itu, dalam konteks penggunaan langsung secara topikal, minyak atsiri melati (MAM) dapat menimbulkan efek iritasi pada kulit. Untuk itu, dalam penelitian ini dikembangkan suatu sistem penghantaran berbasis lipid yakni nanostructured lipid carrier (NLC) sebagai pembawa MAM. Pembuatan NLC-MAM dilakukan dengan metode emulsifikasi-sonikasi. Proses optimasi yang dilakukan meliputi optimasi konsentrasi total lipid, optimasi sistem surfaktan dan konsentrasinya, serta optimasi rasio lipid padat dan lipid cair. Selain itu, dilakukan pula optimasi proses sonikasi dengan memvariasikan tahapan sonikasi. Selanjutnya, formula optimum dikarakterisasi meliputi penentuan ukuran partikel dan distribusinya, pengukuran zeta potensial, pengamatan morfologi partikel, dan penetapan efisiensi enkapsulasi. NLC-MAM yang dihasilkan memiliki bentuk sferis dengan ukuran partikel 152,93 ± 8,18 nm, indeks polidispersitas 0,37 ± 0,05 dan zeta potensial -21,60 ± 6,75 mV. Efisiensi enkapsulasi MAM ke dalam sistem NLC yang diperoleh sebesar 97,65 ± 2,34%, dan tidak mengalami perubahan yang signifikan setelah penyimpanan selama 14 hari. Selanjutnya, potensi aktivitas antioksidan NLC-MAM dievaluasi menggunakan metode peredaman 2,2-diphenyl-1-picrylhydrazyl (DPPH). Hasil yang diperoleh menunjukan bahwa potensi aktivitas antioksidan MAM bebas sebanding dengan MAM yang dienkapsulasi ke dalam sistem NLC. Hal ini menggambarkan bahwa proses pembuatan NLC tidak mempengaruhi potensi aktivitas antioksidan MAM. Selain itu, NLC-MAM yang dihasilkan berpotensi untuk dikembangkan lebih lanjut sebagai agen terapeutik maupun kosmetik

ミトコンドリア薬物送達システムを用いた癌光線力学療法の検証

A non-invasive and specific targeting for cancer therapy is a necessity to manifest in order to minimize the harmful effect on the non-malignant cells. During the past century, photodynamic therapy (PDT) has been actively developed as a non-invasive approach to effectively eradicate the cancer cells with minimal effect on healthy cells. The PDT effect is derived from an energy transfer reaction between light as a source of energy to molecular oxygen, mediated by a light-activated molecule, known as the photosensitizer. The dynamic interaction among these three major components in PDT produces a lethal level of reactive oxygen species (ROS), mainly singlet oxygen. The selectivity of this therapy could be achieved by the specific accumulation of the non-toxic photosensitizer in the tumor region, accompanied by the precise delivery of light in the corresponding area. The singlet oxygen has a highly reactive characteristic that can readily react with several vital molecules in the biological system, resulting in the molecule dysfunction. This interaction may also lead to irreversible oxidative damage and further provoke a lethal effect for the cells. However, the harmful effects of singlet oxygen are restricted by their short lifetime and inadequate diffusion capacity. Therefore, the specific delivery of photosensitizer, mainly in organelle-level, could be a promising strategy to obtain the maximum benefits of this therapy. Moreover, as the important organelle that holds both the vital and lethal functions, mitochondria are identified to be an attractive target for optimizing the PDT outcomes. In the current condition, the existing photosensitizers often manifest disadvantageous features for a practical PDT application. One of them is a non-specific accumulation either in the cellular or at the subcellular level. The other drawback is the inadequate ability of most photosensitizers in absorbing near-infrared (NIR) light. The application of NIR light in PDT, especially in the optical window of biological tissues, is profoundly beneficial because NIR light has an excellent penetration ability toward tissue consisting of water and biomolecules. These problems restrict the use of such compounds in clinical applications. Therefore, the development of a novel PDT system that can fulfill the requirements of the selective organelle accumulation in combination with the long-wavelength light activation is inevitable. The main objective of this research was to construct a novel mitochondrial targeting PDT system with the long-wavelength light activation process. To realize that goal, a synergistic combination between a π-extended porphyrin-type photosensitizer, namely rTPA, and a MITO-Porter system, a versatile mitochondrial targeting liposomal-based nanodevice, was introduced. The incorporation of the rTPA compound into the MITO-Porter system was accomplished using the hydration method with the resulting particle showed a homogenous distribution with a diameter of 157 ± 7 nm and highly positive zeta potentials of 32 ± 3 mV. This novel mitochondrial targeting PDT system, namely the rTPA-MITO-Porter, manifested a robust capacity in producing a high level of singlet oxygen, specifically in the mitochondrial compartment of tumors, during a 700-nm light irradiation process. Based on the cellular uptake and intracellular observation results, most of the rTPA-MITO-Porter particles were efficiently internalized into the cells and concentrated in the mitochondrial compartment of tumors. Furthermore, this system displayed an efficient cytotoxicity profile against two types of human tumor cell lines, namely HeLa cells (human cervical cancer cells) and SAS cells (human squamous cells carcinoma of the tongue), as indicated by the low EC50 value of 0.16 ± 0.02 μM and 0.41 ± 0.18 μM, respectively. Additionally, the apoptosis pathway was actively induced during the PDT process of the rTPA-MITO-Porter, as shown by the formation of apoptotic bodies and fragmentation of mitochondrial structure. Inspired by the excellent cell killing ability during the in vitro experiments, the translation process into the in vivo applications has further proceeded. A slight modification on the rTPA-MITO-Porter formulation, particularly on the helper lipid composition and the total lipids’ concentration, was made without altering the mitochondrial targeting ability and the photo-induced cytotoxic capacity. The remarkable inhibition of the tumor growth was obtained in the SAS cells-bearing mouse model after a single PDT treatment of the rTPA-MITO-Porter with the rTPA dose of 8.2 μg/mouse via intratumoral administration. There was also no significant alteration on the bodyweight of the mice during the treatment, implying the promising in vivo cell-killing ability of this system with a high safety profile. Furthermore, the depolarization on the mitochondrial membrane was observed after the PDT process of the rTPA-MITO-Porter, indicating the damage of mitochondrial membrane due to the specific localization of the photochemical reaction on the mitochondrial compartment of tumors. Finally, the findings presented in this research serve to verify the considerable functions of the MITO-Porter system as the mitochondrial selective drug delivery technology in potentiating the PDT outcomes as well as the importance of mitochondria as the predominant subcellular target for PDT. Moreover, this novel biologically-active nanomaterial manifests an encouraging feature for PDT applications, particularly for the superficial-type cancer cells

ミトコンドリア薬物送達システムを用いた癌光線力学療法の検証 [全文の要約]

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An updated review of Typhonium flagelliforme: phytochemical compound, pharmacological activities and the use of vitexin and isovitexin as flavonoid compound in cosmetics development

Typhonium flagelliforme, a plant known for its medicinal properties, has numerous benefits in the treatment of certain diseases. This comprehensive research provides a detailed review of the phytochemical and pharmacological activities of this plant, with a specific focus on the utilization of its flavonoid compounds, namely vitexin and isovitexin, in the development of cosmetic formulas. The phytochemical compounds include flavonoid, coumaric acid, and other polyphenols compounds. These compounds exhibit a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-cancer, reduced immunosuppressive effects by reducing lymphocyte proliferation, antibacterial, improved immune system activities, and cured gastric ulcers. Based on these pharmacological activities, this research summarizes the utilization of flavonoid compounds, vitexin, and isovitexin, in developing cosmetic preparations. Subsequently, isovitexin has been shown to possess anti-oxidant and anti-inflammatory, and it shares similar pharmacological effects with vitexin, likely due to its similar chemical structure. Considering the excellent antioxidant capacity of isovitexin, there is a favorable opportunity to utilize it in the creation of cosmetic formulations. Therefore, further research is needed to formulate topical preparations and cosmetics containing Typhonium flagelliforme extract

An effective in vivo mitochondria-targeting nanocarrier combined with a pi-extended porphyrin-type photosensitizer

A photochemical reaction mediated by light-activated molecules (photosensitizers) in photodynamic therapy (PDT) causes molecular oxygen to be converted into highly reactive oxygen species (ROS) that are beneficial for cancer therapy. As the active oxygen consumer and the primary regulator of apoptosis, mitochondria are known as an important target for optimizing PDT outcomes. However, most of the clinically used photosensitizers exhibited a poor tumor accumulation profile as well as lack of mitochondria targeting ability. Therefore, by applying a nanocarrier platform, mitochondria-specific delivery of photosensitizers can be materialized. The present research develops an effective mitochondria-targeting liposome-based nanocarrier system (MITO-Porter) encapsulating a pi-extended porphyrin-type photosensitizer (rTPA), which results in a significant in vivo antitumor activity. A single PDT treatment of the rTPA-MITO-Porter resulted in a dramatic tumor inhibition against both human and murine tumors that had been xenografted in a mouse model. Furthermore, depolarization of the mitochondrial membrane was observed, implying the damage of the mitochondrial membrane due to the photochemical reaction that occurred specifically in the mitochondria of tumor cells. The findings presented herein serve to verify the significance of the mitochondria-targeted nanocarrier system for advancing the in vivo PDT effectivity in cancer therapy regardless of tumor type

Fine-tuning the encapsulation of a photosensitizer in nanoparticles reveals the relationship between internal structure and phototherapeutic effects

Photodynamic therapy (PDT) is a cancer therapy that uses a photosensitizer (PS) in the presence of oxygen molecules. Since singlet oxygen is highly reactive, it is important to deliver it to the target site. Thus, an efficient drug delivery system (DDS) is essential for enhancing the efficacy of such a treatment and protecting against the side effects of PDT. Here, we report on attempts to increase the therapeutic effect of PDT by using a DDS, a lipid nanoparticle (LNP). We prepared a porphyrin analog, rTPA (PS) that was encapsulated in LNPs using a microfluidic device. The findings indicated that the internal structure of the prepared particles changed depending on the amount of rTPA in LNPs. The photoactivity and cell-killing effect of PS in LNPs also changed when the amount of the cargo increased. These results suggest that the internal structure of LNPs is important factors that affect drug efficacy