IntroductionAlpha-mangostin is a bi

Introduction
Alpha-mangostin is a biosynthetic di-prenylated tetra-oxygenated
xanthone derivatives [1] which was firstly isolated from the fruit rind
of Garcinia mangostana GM by Schmid in 1855 [2]. Its chemical
structure of 1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-
9H-xanthen-9-one (Figure 1) was elucidated by Yates et al. [3]. Alphamangostin
represented the major active constituent among the detected
xanthones and therefore, it has been considered as analytical marker for
the quality control of GM products [4,5]. Recently, alpha-mangostin
has been commonly employed as ingredient in nutritional supplements,
herbal cosmetics [4] and some topical pharmaceutical preparations [6]
owing to its previously investigated multi-pharmacological activities
that were previously reviewed by Pedraza-Chaverri et al. [7]. It is well
known that alpha-mangostin exhibited a broad spectrum of biological
effects including anti-oxidant [8], anti-inflammatory [9], anti-allergic
[10], analgesic [11], neuro-protective [12], anti-mycobacterial [1], antifungal
[13], anti-bacterial [14] and anti-proliferative [15,16] activities.
In addition, recent studies have indicated that alpha-mangostin
had anti-metastatic effect against various cancer cell lines [17-19].
Nevertheless, the results of pharmacokinetic study of pure alphamangostin
revealed its low oral bioavailability attributed to the first
pass metabolism beside its non-selective distribution into the rat tissue
[20]. As such, we had previously encapsulated the alpha-mangostin into
poly (lactic-co-glycolic acid) PLGA nanospheres in order to enhance
its bioavailability through selective targeting of the compound into
specific tissue. The selectivity is envisaged to be achieved based on
“enhanced permeability and retention” (EPR) effect duly caused by
its size that passively distributed and retained within porous vascular
structure of tumor sites. In addition, the drug delivery employing
PLGA co-polymer that was fabricated into microspheres had long been
used clinically. Zoladex and Lupron were among the popular drugs.
The carrier system was also employed here due to its ability to provide
controlled-release of drugs apart from its biodegradability that do not
warrant second surgery to remove the carrier. Although biodegradable
PLGA microparticles have been widely employed as delivery vehicles
for various macromolecules such as protein [21], peptides [22] and
plasmid DNA [23], numerous small molecules were encapsulated in
order to enhance their therapeutic activities and to minimize their
adverse effects [24].
As part of routine characterization, encapsulation efficiency
of alpha-mangostin was required to be determined and can only
be accomplished following complete dissolution of the polymeric
microsphere. Previously described method [4] for the assay of pure
alpha-mangostin using methanol as solvent could not be applied to
quantify alpha-mangostin from the PLGA microspheres. This was due
to poor solubilising property of the methanol to completely dissolve the
polymeric PLGA. Another study had employed acetonitrile as solvent
to solubilise xanthone and 3-methoxyxanthone encapsulated-PLGA
nanocapsules but there was no report on the analytical validation
[25]. Further analytical methods were established and validated

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PendahuluanAlpha-mangostin adalah prenylated di biosynthetic tetra-oksigenxanton derivatif [1] yang pertama terisolasi dari kulit buahdari Garcinia mangostana GM oleh Schmid pada tahun 1855 [2]. Kimia yangstruktur 1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-satu (gambar 1) terungkap oleh Yates et al. [3]. Alphamangostinmewakili konstituen aktif utama antara terdeteksiHeterolingkar oksigen dan karena itu, ia telah dianggap sebagai penanda analitis untukkontrol kualitas produk GM [4,5]. Baru-baru ini, alpha-mangostintelah sering dimanfaatkan sebagai bahan dalam suplemen gizi,kosmetik herbal [4] dan persiapan farmasi topikal [6]karena kegiatan multi farmakologis sebelumnya diinvestigasiyang sebelumnya ditinjau oleh Pedraza-Chaverri et al. [7]. Ianya baikdiketahui bahwa Alfa-mangostin dipamerkan spektrum yang luas dari biologisEfek termasuk anti-inflamasi anti oksidan [8], [9], anti-alergi[10], analgesik [11], neuro-pelindung [12], anti-mikobakteri [1], antijamur[13], [14] anti-bakteri dan anti-proliferatif kegiatan [15,16].Selain itu, penelitian terbaru mengindikasikan bahwa Alfa-mangostinmemiliki efek anti metastatik terhadap berbagai jalur sel kanker [17-19].Namun demikian, hasil studi pharmacokinetic alphamangostin murnimengungkapkan ketersediaanhayati lisan yang rendah dikaitkan dengan yang pertamalulus metabolisme samping non selektif distribusi ke jaringan tikus[20]. dengan demikian, kami sebelumnya telah dirumuskan alpha-mangostin kenanospheres PLGA Poli (asam laktat-co-glikolat) untuk meningkatkanIts ketersediaanhayati melalui penargetan selektif kompleks kejaringan tertentu. Selektivitas tergambar harus dicapai berdasarkan"ditingkatkan permeabilitas dan retensi" (EPR) efek sepatutnya disebabkan olehukurannya yang pasif didistribusikan dan disimpan dalam berpori vaskularstruktur situs tumor. Selain itu, obat pengiriman mempekerjakanPLGA Co polimer yang direkayasa ke mikrosfer sudah lamadigunakan di klinis. Zoladex dan Lupron adalah di antara obat populer.Operator sistem juga dipekerjakan di sini karena kemampuannya untuk memberikandikendalikan-rilis obat-obatan dari biodegradability nya yang tidakmenjamin operasi kedua untuk menghapus pembawa. Meskipun biodegradablePLGA mikropartikles telah secara luas digunakan sebagai pengiriman kendaraanuntuk berbagai makromolekul seperti protein [21], peptida [22] danplasmid DNA [23], sejumlah kecil molekul dirumuskan dalampesanan untuk meningkatkan kegiatan terapeutik mereka dan untuk meminimalkan merekaefek yang merugikan [24].Sebagai bagian dari rutin karakterisasi, efisiensi enkapsulasidari alpha-mangostin diminta untuk ditentukan dan hanya dapatdicapai setelah pembubaran Polimerikmicrosphere. Sebelumnya dijelaskan metode [4] untuk assay murniAlpha-mangostin menggunakan metanol sebagai pelarut tidak boleh diaplikasikan kepadamengukur alpha-mangostin dari mikrosfer PLGA. Alasannya adalah karenamiskin solubilising milik metanol benar-benar larutPolimerik PLGA. Studi lain telah dipekerjakan asetonitril sebagai pelarutuntuk melarutkan xanton dan 3-methoxyxanthone dikemas-PLGAnanocapsules tetapi ada adalah tidak ada laporan analisis validasi[25]. metode analisis lebih lanjut itu didirikan dan divalidasi