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.

Three-Dimensional Endoscopy-Assisted Excision and Reconstruction for Metastatic Disease of the Dorsal and Lumbar Spine: Early Results

Sergey Lyulin,Pavel Balaev,Koushik Narayan Subramanyam,Denis Ivliev,Abhishek Vasant Mundargi 대한정형외과학회 2022 Clinics in Orthopedic Surgery Vol.14 No.1

Background: The aim of this study was to explore the role of three-dimensional (3D) endoscopy in surgical management of metastatic disease of the dorsal and lumbar spine. Methods: This is a prospective study on 33 patients (15 men and 18 women, mean age of 61.6 ± 8.9 years) with biopsy-proven metastatic disease of the spine managed by sequential/staged posterior decompression-stabilization, followed by 3D endoscopyassisted anterior corpectomy and stabilization with a mesh cage. All patients had significant extradural compression or spinal instability or both. Sixteen patients had neurological deficits. Visual analog scale (VAS), Frenkel grade (neurological deficits), Karnofsky performance status scale, and the 36-item short-form health survey (SF-36) were used for assessment preoperatively and at 3, 6, and 12 months from surgery. Results: At a mean follow-up of 1.7 ± 0.7 years from surgery, 18 patients were alive. VAS showed significant improvement at the latest follow-up compared to preoperative levels (4.39 vs. 6.61, p = 0.001). Karnofsky status did not show any significant improvement. Frenkel grade improved in 5 patients, deteriorated in 4 patients, and remained unchanged in 24 patients. Regarding SF-36 parameters, general health showed deterioration, but role functioning—physical, role functioning—emotional, social functioning, and body pain showed statistically significant improvement. There was no change in physical health, viability, and mental health. Subjectively the surgeons felt better depth perception and smoother surgical experience with the 3D optics technology. The only complication was delayed wound healing in three patients who had a previous history of radiotherapy to the surgical site. Conclusions: 3D endoscopy is a valuable tool in the management of metastatic spinal disease requiring excision and reconstruction using the combined posterior and anterior approaches. These early results warrant confirmation with more data and longer follow-ups.

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>

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.

Chemical processing strategies to obtain sporopollenin exine capsules from multi-compartmental pine pollen

Arun Kumar Prabhakar,Hui Ying Lai,Michael G. Potroz,Michael K. Corliss,박재현,Raghavendra C. Mundargi,조대호,방사익,조남준 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.53 No.-

Pine pollen is widely used in traditional Chinese medicine and has been consumed as a food product for thousands of years. Owing to wind pollination, its pollen grains are composed of a sporoplasmic central cavity along with two empty air sac compartments. While this architectural configuration is evolutionarily optimized for wind dispersal, such features also lend excellent potential for encapsulating materials, especially in the context of preparing sporopollenin exine capsules (SECs). Herein, we systematically evaluated one-pot acid processing methods in order to generate pine pollen SECs that support compound loading. Morphological properties of the SECs were analysed by scanning electron microscopy (SEM) and dynamic imaging particle analysis (DIPA), and protein removal was evaluated by CHN elemental analysis and confocal laser scanning microscopy (CLSM). It was identified that 5-h acidolysis with 85% w/v phosphoric acid at 70 C yielded an optimal balance of high protein removal and preservation of microcapsule architecture, while other processing methods were also feasible with an additional enzymatic step. Importantly, the loading efficiency of the pine pollen SECs was three-times greater than that of natural pine pollen, highlighting their potential for microencapsulation. Taken together, our findings outline a successful strategy to prepare intact pine pollen SECs and demonstrate for the first time that SECs can be prepared from multi-compartmental pollen capsules, opening the door to streamlined processing approaches to utilize pine pollen microcapsules in industrial applications.

Chemical processing strategies to obtain sporopollenin exine capsules from multi-compartmental pine pollen

Prabhakar, A.K.,Lai, H.Y.,Potroz, M.G.,Corliss, M.K.,Park, J.H.,Mundargi, R.C.,Cho, D.,Bang, S.I.,Cho, N.J. Korean Society of Industrial and Engineering Chemi 2017 Journal of industrial and engineering chemistry Vol.53 No.-

Pine pollen is widely used in traditional Chinese medicine and has been consumed as a food product for thousands of years. Owing to wind pollination, its pollen grains are composed of a sporoplasmic central cavity along with two empty air sac compartments. While this architectural configuration is evolutionarily optimized for wind dispersal, such features also lend excellent potential for encapsulating materials, especially in the context of preparing sporopollenin exine capsules (SECs). Herein, we systematically evaluated one-pot acid processing methods in order to generate pine pollen SECs that support compound loading. Morphological properties of the SECs were analysed by scanning electron microscopy (SEM) and dynamic imaging particle analysis (DIPA), and protein removal was evaluated by CHN elemental analysis and confocal laser scanning microscopy (CLSM). It was identified that 5-h acidolysis with 85% w/v phosphoric acid at 70<SUP>o</SUP>C yielded an optimal balance of high protein removal and preservation of microcapsule architecture, while other processing methods were also feasible with an additional enzymatic step. Importantly, the loading efficiency of the pine pollen SECs was three-times greater than that of natural pine pollen, highlighting their potential for microencapsulation. Taken together, our findings outline a successful strategy to prepare intact pine pollen SECs and demonstrate for the first time that SECs can be prepared from multi-compartmental pollen capsules, opening the door to streamlined processing approaches to utilize pine pollen microcapsules in industrial applications.