Capecitabine Pattern of Usage, Rate of Febrile Neutropaenia and Treatment Related Death in Asian Cancer Patients in Clinical Practice

Phua, Vincent Chee Ee,Wong, Wei Quan,Tan, Pei Lin,Bustam, Anita Zarina,Saad, Marniza,Alip, Adlinda,Ishak, Wan Zamaniah Wan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

Background: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from $1^{st}$ January 2009 till $31^{st}$ June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. Results: Between $1^{st}$ January 2009 and $30^{th}$ June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. Conclusions: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.

Encapsulation and controlled release formulations of 5-fluorouracil from natural Lycopodium clavatum spores

Raghavendra C. Mundargi,Ee-Lin Tan,Jeongeun Seo,조남준 한국공업화학회 2016 Journal of Industrial and Engineering Chemistry Vol.36 No.-

Cost effective, uniform-size multiparticulate formulations of the chemotherapeutic agent 5-fluorouracil(5-FU) loaded in natural Lycopodium clavatum spores were developed by three different encapsulationtechniques: passive, compression and vacuum loading. The surface morphology, and micromeriticproperties of 5-FU spore formulations were characterized by scanning electron microscopy and dynamicimage particle analysis, respectively. The encapsulation efficiency of spores by vacuum-assisted loadingwas higher (49%) compared to passive and compression loading techniques. The vacuum-loadedformulation was selected for further development with a Eudragit RS 100 (EUD) coating that enabledcontrolled 5-FU release in simulated gastric (pH 1.2) and intestinal (pH 7.4) conditions. The surfacemorphology analysis after EUD coating at two different EUD concentrations (2.5% w/v and 10% w/v)indicates that a thin, conformal layer of EUD was deposited on the spore surface. The in-vitro release of 5-FU from coated spores exhibited a slower release profile compared to uncoated spores, and was extendedfor up to 30 h in simulated gastrointestinal conditions. Collectively, the findings demonstrate that EUDcoated 5-FU loaded natural L. clavatum spores provide a controlled release formulation that would aidtreatment options against gastrointestinal cancer and other related maladies.

Macromolecular Microencapsulation Using Pine Pollen: Loading Optimization and Controlled Release with Natural Materials

Prabhakar, Arun K.,Potroz, Michael G.,Tan, Ee-Lin,Jung, Haram,Park, Jae Hyeon,Cho, Nam-Joon American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.34

<P>Pine pollen offers an all-natural multicavity structure with dual hollow air sacs, providing ample cargo capacity available for compound loading. However, the pollen exhibits reduced permeability because of the presence of a thin natural water-proofing layer of lipidic compounds. Herein, we explore the potential for compound loading within pine pollen and the potential for developing all-natural formulations for targeted delivery to the intestinal tract. Removal of the surface-adhered lipidic compounds is shown to improve surface wetting, expose nanochannel structures in the outer pollen shell and enhance water uptake throughout the whole pollen structure. Optimization of loading parameters enabled effective compound loading within the outer pollen shell sexine structure, with bovine serum albumin (BSA) serving as a representative protein. All-natural oral delivery formulations for targeted intestinal delivery are developed based on tableting of BSA-loaded defatted pine pollen, with the incorporation of xanthan gum as a natural binder, or ionotropically cross-linked sodium alginate as an enteric coating. Looking forward, the large cargo capacity, ease of compound loading, competitive cost, abundant availability, and extensive historical usage as food and medicine make pine pollen an attractive microencapsulant for a wide range of potential applications.</P> [FIG OMISSION]</BR>

Preserving the inflated structure of lyophilized sporopollenin exine capsules with polyethylene glycol osmolyte

Michael K. Corliss,Chuan Kiat Bok,Jurriaan Gillissen,Michael G. Potroz,정하람,Ee-Lin Tan,Raghavendra C. Mundargi,조남준 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.61 No.-

Extracted from natural pollen grains, sporopollenin exine capsules (SECs) are robust, chemically inert biopolymer shells that posess highly uniform size and shape characteristics and that can be utilized as hollow microcapsules for drug delivery applications. However, it is challenging to extract fully functional SECs from many pollen species because pollen grains often collapse, causing the loss of architectural features, loading volume, and bulk uniformity. Herein, we demonstrate that polyethylene glycol (PEG) osmolyte solutions can help preserve the native architectural features of extracted SECs, yielding inflated microcapsules of high uniformity that persist even after subsequent lyophilization. Optimal conditions were first identified to extract SECs from cattail (Typhae angustfolia) pollen via phosphoric acid processing after which successful protein removal was confirmed by elemental (CHN), mass spectrometry (MALDI-TOF), and confocal laser canning microscopy (CLSM) analyses. The shape of SECs was then assessed by scanning electron microscopy (SEM) and dynamic image particle analysis (DIPA). While acid-processed SECs experienced high degrees of structural collapse, incubation in 2.5% or higher PEG solutions significantly improved preservation of spherical SEC shape by inducing inflation within the microcapsules. A theoretical model of PEG-induced osmotic pressure effects was used to interpret the experimental data, and the results show excellent agreement with the known mechanical properties of pollen exine walls. Taken together, these findings demonstrate that PEG osmolyte is a useful additive for preserving particle shape in lyophilized SEC formulations, opening the door to broadly applicable strategies for stabilizing the structure of hollow microcapsules.

Preserving the inflated structure of lyophilized sporopollenin exine capsules with polyethylene glycol osmolyte

Corliss, Michael K.,Bok, Chuan Kiat,Gillissen, Jurriaan,Potroz, Michael G.,Jung, Haram,Tan, Ee-Lin,Mundargi, Raghavendra C.,Cho, Nam-Joon THE KOREAN SOCIETY OF INDUSTRIAL AND ENGINEERING 2018 JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY -S Vol.61 No.-

<P><B>Abstract</B></P> <P>Extracted from natural pollen grains, sporopollenin exine capsules (SECs) are robust, chemically inert biopolymer shells that posess highly uniform size and shape characteristics and that can be utilized as hollow microcapsules for drug delivery applications. However, it is challenging to extract fully functional SECs from many pollen species because pollen grains often collapse, causing the loss of architectural features, loading volume, and bulk uniformity. Herein, we demonstrate that polyethylene glycol (PEG) osmolyte solutions can help preserve the native architectural features of extracted SECs, yielding inflated microcapsules of high uniformity that persist even after subsequent lyophilization. Optimal conditions were first identified to extract SECs from cattail (<I>Typhae angustfolia</I>) pollen <I>via</I> phosphoric acid processing after which successful protein removal was confirmed by elemental (CHN), mass spectrometry (MALDI-TOF), and confocal laser canning microscopy (CLSM) analyses. The shape of SECs was then assessed by scanning electron microscopy (SEM) and dynamic image particle analysis (DIPA). While acid-processed SECs experienced high degrees of structural collapse, incubation in 2.5% or higher PEG solutions significantly improved preservation of spherical SEC shape by inducing inflation within the microcapsules. A theoretical model of PEG-induced osmotic pressure effects was used to interpret the experimental data, and the results show excellent agreement with the known mechanical properties of pollen exine walls. Taken together, these findings demonstrate that PEG osmolyte is a useful additive for preserving particle shape in lyophilized SEC formulations, opening the door to broadly applicable strategies for stabilizing the structure of hollow microcapsules.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Identified that polyethylene glycol (PEG) osmolyte can prevent SEC particle collapse. </LI> <LI> Chemical route to extract SECs from cattail pollen was achieved successfully. </LI> <LI> Model of PEG-induced osmotic pressure effects agrees with experimental data. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>