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Fulltext Insulin-Loaded Barium Salt Particles Facilitate Oral Delivery of Insulin in Diabetic Rats

Zaman R, Karim ME, Othman I, Zaini A, Chowdhury EH

Pharmaceutics, 2020 Jul 29;12(8).
PMID: 32751231 DOI: 10.3390/pharmaceutics12080710

Oral delivery is considered as the most preferred and yet most challenging mode of drug administration; especially a fragile and sensitive peptide like insulin that shows extremely low bioavailability through the gastro-intestinal (GIT) route. To address this problem, we have designed a novel drug delivery system (DDS) using precipitation-induced Barium (Ba) salt particles. The DDS can load insulin molecules and transport them through the GIT route. There were several in vitro simulation tests carried out to prove the efficiency of Ba salt particles as oral delivery candidates. All three Ba salt particles (BaSO4, BaSO3, and BaCO3) showed very good loading of insulin (>70% in all formulations) and a degree of resistance throughout a wide range of pHs from basic to acidic conditions when assessed by spectrophotometry. Particles and insulin-associated particles were morphologically assessed and characterized using FE-SEM and FT-IR. A set of tests were designed and carried out with mucin to predict whether the particles are potentially capable of overcoming one of the barriers for crossing intestinal epithelium. The mucin binding experiment demonstrated 60-100% of mucin adhesion to the three different particles. FT-IR identifies the characteristic peaks for mucin protein, particles, and particle-mucin complex re-confirming mucin adhesion to the particles. Finally, the effectiveness of nano-insulin was tested on streptozotocin (STZ) induced diabetic rats. A short acting human insulin analog, insulin aspart, was loaded into Ba salt particles at a dose of 100 IU/Kg prior to oral administration. Among the three formulations, insulin aspart-loaded BaSO4 and BaCO3 particles dramatically reduced the existing hyperglycemia. BaSO4 with loaded Insulin showed an onset of glucose-lowering action within 1 hr, with blood glucose level measured significantly lower compared to the 2nd and 3rd h (p < 0.05). Insulin-loaded BaCO3 particles showed a significant decrease in blood glucose level at 1-2 h, although the glucose level started to show a slight rise at 3rd h and by 4th h, it was back to baseline level. However, although BaSO3 particles with loaded insulin showed a trend of reduction in blood glucose level, the reduction was not found to be significant (p < 0.05) at any point in time. Therefore, oral formulations of insulin/BaSO4 and insulin/BaCO3 particles were observed as effective as native insulin aspart subcutaneous formulation in terms of onset and duration of action. Further investigation will be needed to reveal bioavailability and mechanism of action of this novel Nano-Insulin formulations.

Matched MeSH terms: Biological Availability
Wound Healing Property of Curcuminoids as a Microcapsule-Incorporated Cream

Ang LF, Darwis Y, Koh RY, Gah Leong KV, Yew MY, Por LY, et al.

Pharmaceutics, 2019 May 01;11(5).
PMID: 31052413 DOI: 10.3390/pharmaceutics11050205

Curcuminoids have been used for the management of burns and wound healing in traditional Chinese medicine practices but the wide application of curcuminoids as a healing agent for wounds has always been a known problem due to their poor solubility, bioavailability, colour staining properties, as well as due to their intense photosensitivity and the need for further formulation approaches to maximise their various properties in order for them to considerably contribute towards the wound healing process. In the present study, a complex coacervation microencapsulation was used to encapsulate curcuminoids using gelatin B and chitosan. This study also focused on studying and confirming the potential of curcuminoids in a microencapsulated form as a wound healing agent. The potential of curcuminoids for wound management was evaluated using an in vitro human keratinocyte cell (HaCaT) model and the in vivo heater-inflicted burn wound model, providing evidence that the antioxidant activities of both forms of curcuminoids, encapsulated or not, are higher than those of butylated hydroxyanisole and butylated hydroxytoluene in trolox equivalent antioxidant capacity (TEAC) and (2,2-diphenyl-1-picryl-hydrazyl-hydrate) (DPPH) studies. However, curcuminoids did not have much impact towards cell migration and proliferation in comparison with the negative control in the in vitro HaCaT study. The micoencapsulation formulation was shown to significantly influence wound healing in terms of increasing the wound contraction rate, hydroxyproline synthesis, and greater epithelialisation, which in turn provides strong justification for the incorporation of the microencapsulated formulation of curcuminoids as a topical treatment for burns and wound healing management as it has the potential to act as a crucial wound healing agent in healthcare settings.

Matched MeSH terms: Biological Availability
Diosgenin, a steroidal saponin, and its analogs: Effective therapies against different chronic diseases

Parama D, Boruah M, Yachna K, Rana V, Banik K, Harsha C, et al.

Life Sci, 2020 Nov 01;260:118182.
PMID: 32781063 DOI: 10.1016/j.lfs.2020.118182

BACKGROUND: Chronic diseases are a major cause of mortality worldwide, and despite the recent development in treatment modalities, synthetic drugs have continued to show toxic side effects and development of chemoresistance, thereby limiting their application. The use of phytochemicals has gained attention as they show minimal side effects. Diosgenin is one such phytochemical which has gained importance for its efficacy against the life-threatening diseases, such as cardiovascular diseases, cancer, nervous system disorders, asthma, arthritis, diabetes, and many more.
AIM: To evaluate the literature available on the potential of diosgenin and its analogs in modulating different molecular targets leading to the prevention and treatment of chronic diseases.
METHOD: A detailed literature search has been carried out on PubMed for gathering information related to the sources, biosynthesis, physicochemical properties, biological activities, pharmacokinetics, bioavailability and toxicity of diosgenin and its analogs.
KEY FINDINGS: The literature search resulted in many in vitro, in vivo and clinical trials that reported the efficacy of diosgenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK, etc., which play a crucial role in the development of most of the diseases. Reports have also revealed the safety of the compound and the adaptation of nanotechnological approaches for enhancing its bioavailability and pharmacokinetic properties.
SIGNIFICANCE: Thus, the review summarizes the efficacy of diosgenin and its analogs for developing as a potent drug against several chronic diseases.

Matched MeSH terms: Biological Availability
Fulltext Gliclazide loaded PLGA-HPMC second generation nanocrystals for oral delivery: design, development and in vitro performance characterization

Krishnamoorthy R., Bibhu Prasad Panda, Shivashekaregowda N. K. H., Low B. S., Bhattamisra S. K.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):44-44.
MyJurnal

Introduction: Second generation functionalized nanocrystal is the advancement of nanocrystal technology with great potential to accommodate BCS (Biopharmaceutical Classification System) class II drugs to meet their formulation and drug delivery challenges. Gliclazide is a BCS class II drug used in the treatment of type 2 diabetes, shows poor water solubility and low rate of dissolution, leads to poor and variable oral bioavailability. The second generation poly(D,L-lactide-co-glycolide) (PLGA) Hydroxypropyl methylcellulose (HPMC) based functionalized nanocrystals of gliclazide were prepared by a combination method of emulsion diffusion-high pressure homogenization-solvent evaporation. Methods: Gliclazide second generation nanocrystals were fabricated with taguchi orthogonal experimental design in combination of step up and top down nanoformulation strategies using drug-polymer (PLGA) ratio at 1:0.5, 1:0.75, 1:1 with HPMC(0.5, 0.75, 1% w/v) as stabilizer. The formulated gliclazide PLGA-HPMC nanocrystals were investigated on particle size, polydispersity index, zeta potential, solubility study, drug entrapment efficiency, in vitro drug release, and surface morphology and compatibility studies. The gliclazide PLGA nanocrystals formulation was prepared with Drug : PLGA at 1: 1 ratio with concentrations 0.75% w/v HPMC at 5 homogenization cycles with 1000bar produce optimized gliclazide nanocrystals. Results: The optimized MSGNC8 formulation
showed particle size of 239.9 nm, entrapment efficiency 98.62%, and drug release of 43.75%, 82.12% and 98.08% at 3hrs, 24hrs, and 48hrs compared to pure gliclazide % drug release of 28.73%, 67.51% and 78.41% at 3hrs, 24hrs, 48hrs respectively. The solubility study of optimized formulation shows eight folds increased in saturation solubility compared to pure drug. Scanning electron microscopy (SEM) analysis of the gliclazide nanocrystals revealed that
gliclazide retained its crystal morphology in polymeric nanocrystals. Further, fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies on gliclazide PLGA-HPMC nanocrystals emphasize drug and excipient compatibility in development of gliclazide nanocrystals. Conclusion: The potential outcomes of research findings emphasize that the developed gliclazide second-generation nanocrystals, which resulted in increase in drug solubility and rate of dissolution with delayed modified release, can be explored in delivery of gliclazide for type 2 diabetes management.

Matched MeSH terms: Biological Availability
Smart pH-responsive co-polymeric hydrogels for controlled delivery of capecitabine: Fabrication, Optimization and in vivo toxicology screening

Rehman U, Sarfraz RM, Mahmood A, Hussain Z, Thu HE, Zafar N, et al.

Curr Drug Deliv, 2021 Feb 11.
PMID: 33583374 DOI: 10.2174/1567201818666210212085912

BACKGROUND: Despite exhibiting promising anticancer potential, the clinical significance of capecitabine (a potent prodrug of 5-fluorouracil used for treatment of colorectal cancer) is limited owing to its acidic and enzymatic hydrolysis, lower absorption following the oral administration, poor bioavailability, short plasma half-life and poor patient compliance.
OBJECTIVES: The present study was aimed to fabricate the capecitabine as smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media.
METHODS: The smart pH sensitive HP-β-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination.
RESULTS: The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. Capecitabine loading was ranged from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%) was seen at pH 7.4. Based upon regression coefficient R2 (0.96 - 0.99) best fit model was zero order. The extensive toxicity evaluations evidenced good safety profile with no signs of oral, dermal or ocular toxicities, as well as no variations in blood parameters and histology of vital organs.
CONCLUSION: Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as pH-responsive system for controlled delivery of anticancer agents.

Matched MeSH terms: Biological Availability
Fulltext Optimisation of the production of fish gelatine nanoparticles as a carrier for sunflower-derived biopeptide

Akbar, I., Jaswir, I., Jamal, P.

International Food Research Journal, 2020;27(1):171-181.
MyJurnal

Gelatine obtained from fish skin has become a potential source of preparing nanoparticles and
encapsulation of bioactive compounds. Within these fish skin, gelatine nanoparticles show
potent benefits for application in pharmaceutical and cosmetic industry. The encapsulated
bioactive ingredients within nanoparticles have improved bioavailability, delivery properties,
and solubility of the nutraceuticals within the human body and blood stream. Many of such
bioactive peptides (biopeptides) are potent antioxidants; and as oxidative stress is the main
cause of the onset of various chronic diseases, encapsulation of antioxidant biopeptides within
fish gelatine nanoparticles could be a potential remedy to prevent or delay the onset of such
diseases and for better health prospects. The purpose of the present work was to prepare a
simple, safe, and reproducible novel food delivery nanoparticle system encapsulating a desirable antioxidant biopeptide. An optimisation study was conducted to produce a desirable size
of gelatine nanoparticles which showed a higher encapsulation efficiency of an antioxidant
biopeptide. Sunflower biopeptide was chosen as the antioxidant biopeptide, as the activity of
this protein hydrolysate is quite high at DPPH of 89% and FRAP assay of 968 µm/L. Tilapia
fish was used as gelatine source at an average yield of the process at 10% wt/wt. Effects of
parameters such as pH, biopeptide concentration, and cross-linking agent ‘glutaraldehyde’ on
the size, stability, and encapsulation efficiency on the nanoparticles were studied. The average
diameter of the biopeptide loaded gelatine nanoparticle was between 228.3 and 1,305 nm.
Encapsulation efficiency was 76% at an optimal pH of 2, glutaraldehyde concentration of 2
mL, and biopeptide concentration of 0.1 mg/mL exhibited DPPH at 92% and FRAP assay of
978 µm/L. To understand the absorption of sunflower biopeptide in stomach, blood stream,
and biopeptide release of the gelatine nanoparticles, biopeptide loaded gelatine nanoparticles
were subjected to simulated gastrointestinal conditions mimicking human stomach and
intestine; and showed peptide release of 0.1464 and 0.277 mg/mL upon pepsin and pancreatin
digestion, respectively.

Matched MeSH terms: Biological Availability
Fulltext Development and Evaluation of 1'-Acetoxychavicol Acetate (ACA)-Loaded Nanostructured Lipid Carriers for Prostate Cancer Therapy

Subramaniam B, Arshad NM, Malagobadan S, Misran M, Nyamathulla S, Mun KS, et al.

Pharmaceutics, 2021 Mar 24;13(4).
PMID: 33804975 DOI: 10.3390/pharmaceutics13040439

1'-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.

Matched MeSH terms: Biological Availability
Fulltext Date palm and goat milk improve haematological parameters and availability of functional iron in iron deficient rats

Nurainna Abd Majid, Zuriani Zainol, Nor Aripin Shamaan, Nazefah Abd Hamid, Nuruliza Roslan, Noor Fadzilah Zulkifli

Malaysian Journal of Medicine and Health Sciences, 2020;16(3):52-59.
MyJurnal

Introduction: Iron deficiency anaemia (IDA) is endemic especially in the under-developed and developing countries and is a major public health concern. Improving nutrition is one of the ways to alleviate this condition. Consumption of locally available and affordable food such as date palm and goat milk which are rich in iron is one of the ways to overcome IDA. This study is aimed at evaluating the effect of date palm and goat milk supplementation on hae- matological parameters and iron bioavailability in IDA rats. Methods: 24 male Wistar rats were randomly divided into normal control and IDA group. The normal control was fed with normal diet and water ad libitum while the IDA group were fed on iron-deficient diet for two weeks to induce iron deficiency. The IDA rats were further divided into subgroups; each being supplemented with date palm, goat milk, a combination of date palm and goat milk, and ferrous fumarate as positive control. Blood were collected after 28 days for haematological parameters and iron profile determination. Iron bioavailability was assessed using the haemoglobin regeneration efficiency (HRE) index. Data was analysed by Student T Test and ANOVA using SPSS 23.0 software with p value < 0.05 considered as sta- tistically significant. Results: Supplementation of date palm and goat milk for 28 days significantly improved Hb, RBC, PCV, MCV, MCH, serum iron and transferrin saturation (p

Matched MeSH terms: Biological Availability
Fulltext Immunomodulatory Effects and Mechanisms of Curcuma Species and Their Bioactive Compounds: A Review

Yuandani, Jantan I, Rohani AS, Sumantri IB

Front Pharmacol, 2021;12:643119.
PMID: 33995049 DOI: 10.3389/fphar.2021.643119

Curcuma species (family: Zingiberaceae) are widely utilized in traditional medicine to treat diverse immune-related disorders. There have been many scientific studies on their immunomodulating effects to support their ethnopharmacological uses. In this review, the efficacy of six Curcuma species, namely, C. longa L., C. zanthorrhiza Roxb., C. mangga Valeton & Zijp, C. aeruginosa Roxb. C. zedoaria (Christm.) Roscoe, and C. amada Roxb., and their bioactive metabolites to modulate the immune system, their mechanistic effects, and their potential to be developed into effective and safe immunomodulatory agents are highlighted. Literature search has been carried out extensively to gather significant findings on immunomodulating activities of these plants. The immunomodulatory effects of Curcuma species were critically analyzed, and future research strategies and appropriate perspectives on the plants as source of new immunomodulators were discussed. Most of the pharmacological investigations to evaluate their immunomodulatory effects were in vivo and in vitro experiments on the crude extracts of the plants. The extracts were not chemically characterized or standardized. Of all the Curcuma species investigated, the immunomodulatory effects of C. longa were the most studied. Most of the bioactive metabolites responsible for the immunomodulating activities were not determined, and mechanistic studies to understand the underlying mechanisms were scanty. There are limited clinical studies to confirm their efficacy in human. Of all the bioactive metabolites, only curcumin is undergoing extensive clinical trials based on its anti-inflammatory properties and main use as an adjuvant for the treatment of cancer. More in-depth studies to understand the underlying mechanisms using experimental in vivo animal models of immune-related disorders and elaborate bioavailability, preclinical pharmacokinetics, and toxicity studies are required before clinical trials can be pursued for development into immunomodulatory agents.

Matched MeSH terms: Biological Availability
Oral Nanoemulsion of Fenofibrate: Formulation, Characterization, and In Vitro Drug Release Studies

Gulati N, Kumar Chellappan D, M Tambuwala M, A A Aljabali A, Prasher P, Kumar Singh S, et al.

Assay Drug Dev Technol, 2021 05 14;19(4):246-261.
PMID: 33989048 DOI: 10.1089/adt.2021.012

Nanoemulsions (NMs) are one of the most important colloidal dispersion systems that are primarily used to improve the solubility of poorly water soluble drugs. The main objectives of this study were, first, to prepare an NM loaded with fenofibrate using a high shear homogenization technique and, second, to study the effect of variable using a central composite design. Twenty batches of fenofibrate-loaded NM formulations were prepared. The formed NMs were subjected to droplet size analysis, zeta potential, entrapment efficiency, pH, dilution, polydispersity index, transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry, differential scanning calorimetry (DSC), and in vitro drug release study. Analysis of variance was used for entrapment efficiency data to study the fitness and significance of the design. The NM-7 batch formulation demonstrated maximum entrapment efficiency (81.82%) with lowest droplet size (72.28 nm), and was thus chosen as the optimized batch. TEM analysis revealed that the NM was well dispersed with droplet sizes <100 nm. Incorporation of the drug into the NM was confirmed with DSC studies. In addition, the batch NM-7 also showed the maximum in vitro drug release (87.6%) in a 0.05 M sodium lauryl sulfate solution. The release data revealed that the NM followed first-order kinetics. The outcomes of the study revealed the development of a stable oral NM containing fenofibrate using the high shear homogenization technique. This approach may aid in further enhancing the oral bioavailability of fenofibrate, which requires further in vivo studies.

Matched MeSH terms: Biological Availability
Composition, sources, and bioavailability of nitrogen in a longitudinal gradient from freshwater to estuarine waters

Jani J, Toor GS

Water Res, 2018 06 15;137:344-354.
PMID: 29571112 DOI: 10.1016/j.watres.2018.02.042

Nitrogen (N) transport from land to water is a dominant contributor of N in estuarine waters leading to eutrophication, harmful algal blooms, and hypoxia. Our objectives were to (1) investigate the composition of inorganic and organic N forms, (2) distinguish the sources and biogeochemical mechanisms of nitrate-N (NO3-N) transport using stable isotopes of NO3- and Bayesian mixing model, and (3) determine the dissolved organic N (DON) bioavailability using bioassays in a longitudinal gradient from freshwater to estuarine ecosystem located in the Tampa Bay, Florida, United States. We found that DON was the most dominant N form (mean: 64%, range: 46-83%) followed by particulate organic N (PON, mean: 22%, range: 14-37%), whereas inorganic N forms (NOx-N: 7%, NH4-N: 7%) were 14% of total N in freshwater and estuarine waters. Stable isotope data of NO3- revealed that nitrification was the main contributor (36.4%), followed by soil and organic N sources (25.5%), NO3- fertilizers (22.4%), and NH4+ fertilizers (15.7%). Bioassays showed that 14 to 65% of DON concentrations decreased after 5-days of incubation indicating utilization of DON by microbes in freshwater and estuarine waters. These results suggest that despite low proportion of inorganic N forms, the higher concentrations and bioavailability of DON can be a potential source of N for algae and bacteria leading to water quality degradation in the estuarine waters.

Matched MeSH terms: Biological Availability
Fulltext Folate content and availability in Malaysian cooked foods

Chew SC, Khor GL, Loh SP

Malays J Nutr, 2012 Dec;18(3):383-91.
PMID: 24568079 MyJurnal

Data on folate availability of Malaysian cooked foods would be useful for estimation of dietary folate intake; however such information is scarce.

Matched MeSH terms: Biological Availability
Simple high-performance liquid chromatographic method for the determination of metformin in human plasma

Kah Hay Yuen, Kok Khiang Peh

J Chromatogr B Biomed Sci Appl, 1998 Jun 12;710(1-2):243-6.
PMID: 9686895

A simple high-performance liquid chromatographic method using ultraviolet detection was developed for the determination of metformin in human plasma. The method entailed direct injection of the plasma sample after deproteination using perchloric acid. The mobile phase comprised 0.01 M potassium dihydrogen orthophosphate (pH 3.5) and acetonitrile (60:40, v/v). Analyses were run at a flow-rate of 1.0 ml/min with the detector operating at a detection wavelength of 234 nm. The method is specific and sensitive, with a quantification limit of approximately 60 ng/ml and a detection limit of 15 ng/ml at a signal-to-noise ratio of 3:1. The mean absolute recovery value was about 97%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 8%. The calibration curve was linear over a concentration range of 62.5-4000 ng/ml.

Matched MeSH terms: Biological Availability
Simple high-performance liquid chromatographic method for the determination of acyclovir in human plasma using fluorescence detection

Peh KK, Yuen KH

J Chromatogr B Biomed Sci Appl, 1997 May 23;693(1):241-4.
PMID: 9200543

A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of acyclovir in human plasma. The method entailed direct injection of the plasma sample after deproteination. It is both specific and sensitive with a detection limit of 30 ng/ml at a signal-to-noise ratio of 3:1, and is thus suitable for use in pharmacokinetic studies of acyclovir. The method had a mean absolute recovery of 96%, while the within-day and between-day coefficients of variation and percentages error were all less than 8%. The calibration curve was linear over a concentration range of 62.5-4000 ng/ml.

Matched MeSH terms: Biological Availability
Simple high-performance liquid chromatographic method for determination of ketoconazole in human plasma

Yuen KH, Peh KK

J Chromatogr B Biomed Sci Appl, 1998 Sep 18;715(2):436-40.
PMID: 9792531

A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of ketoconazole in human plasma. The method entailed direct injection of the plasma sample after deproteinization using acetonitrile. The mobile phase comprised 0.05 M disodium hydrogen orthophosphate and acetonitrile (50:50, v/v) adjusted to pH 6. Analysis was run at a flow-rate of 1.5 ml/min with the detector operating at an excitation wavelength of 260 nm and an emission wavelength of 375 nm. The method is specific and sensitive with a quantification limit of approximately 60 ng/ml and a detection limit of 40 ng/ml at a signal-to-noise ratio of 3:1. Mean absolute recovery value was about 105%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 14%. The calibration curve was linear over a concentration range of 62.5-8000 ng/ml.

Matched MeSH terms: Biological Availability
Improved bioavailability of vitamin E with a self emulsifying formulation

Julianto T, Yuen KH, Noor AM

Int J Pharm, 2000 Apr 25;200(1):53-7.
PMID: 10845685

A single dose study was conducted to evaluate the bioavailability of a novel self-emulsifying vitamin E preparation, in comparison with that of a commercial product, Natopherol, available as soft gelatin capsules under fasted condition. The self-emulsifying preparation achieved a faster rate and higher extent of absorption. A statistically significant difference was observed between the values of the two preparations in the parameters AUC, Cmax and Tmax. Moreover, the 90% confidence interval of the logarithmic transformed AUC values of the self-emulsifying preparation over those of the soft gelatin capsule product was found to be between 2.1 and 4.1, suggesting an increase in bioavailability of between 210 and 410%. As for Cmax, the 90% confidence interval was between 2.1 and 3.0. However, no statistically significant difference was observed between the t(1/2) values estimated from the plasma concentration versus time data of the two preparations. The values are also comparable to those reported in the literature.

Matched MeSH terms: Biological Availability
Improved oral bioavailability of artemisinin through inclusion complexation with beta- and gamma-cyclodextrins

Wong JW, Yuen KH

Int J Pharm, 2001 Oct 04;227(1-2):177-85.
PMID: 11564552

The bioavailability of beta- and gamma-cyclodextrin artemisinin complexes was evaluated in comparison with a normal commercially available preparation, Artemisinin 250. Twelve healthy male volunteers participated in the study conducted according to a three-way crossover design. The bioavailability was compared using the parameters, total area under the plasma level-time curve (AUC(0-infinity)), peak plasma concentration (C(max)), and time to reach peak plasma concentration (T(max)). A statistically significant difference was observed between the values of the complexes and Artemisinin 250 for the three parameters. However, no statistically significant difference was observed between the values of the beta- and gamma-cyclodextrin complexes. Moreover, the 90% confidence interval for the ratio of the AUC(0-infinity) values of the beta-cyclodextrin complex over those of Artemisinin 250 was estimated to be between 1.51-2.04, while that of C(max) was between 1.73-2.93. For the gamma-cyclodextrin complex, the respective intervals were 1.30-1.76 and 1.43-2.43. These findings indicated that the beta- and gamma-cyclodextrin complexes had a much higher rate and extent of bioavailability compared to Artemisinin 250. In addition, the absorption of artemisinin was observed to be poor and negligible when the preparations started to arrive in the colon. This could be attributed to poor dissolution of artemisinin in the semi-solid faecal matter in the lower part of the gastrointestinal tract.

Matched MeSH terms: Biological Availability
New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and Future Prospects

Ei Thu H, Hussain Z, Shuid AN

Curr Drug Targets, 2018;19(8):865-876.
PMID: 27894237 DOI: 10.2174/1389450117666161125174625

Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents.

Matched MeSH terms: Biological Availability
The Medicinal Uses, Toxicities and Anti-inflammatory Activity of Polyalthia Species (Annonaceae)

Yao LJ, Jalil J, Attiq A, Hui CC, Zakaria NA

J Ethnopharmacol, 2018 Oct 11.
PMID: 30316887 DOI: 10.1016/j.jep.2018.10.001

ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia is one of the largest and notable genera in Annonaceae family. Polyalthia species have been widely used in folklore medicine for the treatment of rheumatic fever, gastrointestinal ulcer and generalized body pain. Numerous in vitro and in vivo studies on Polyalthia Species have also corroborated the significant anti-inflammatory potential of its extracts and secondary metabolites.
AIM OF THE STUDY: This review is an attempt to assess the anti-inflammatory activity of Polyalthia species by giving critical appraisal and establishing evidences of their traditional uses. Moreover this review will highlight the lead compounds for future drug development that can serve as a potential anti-inflammatory drug with comparative efficacy and minimum side effects.
MATERIALS AND METHODS: An extensive literature review, focusing the anti-inflammatory potential of Polyalthia species was conducted using the following databases: PubMed, ScienceDirect, SpringerLink, Ovid, Scopus and ProQuest, as well as the locally available books, journals and relevant documents. The reference lists of retrieved papers were also searched for additional studies.
RESULTS: The Polyalthia species have shown significant anti-inflammatory activity through various mechanism of action. The most significant anti-inflammatory mechanism includes the inhibition of nuclear factor kappa B (NF-κB), prostaglandins (PGs), pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS). The data suggests that hydroxycleroda-3,13-dien-15,16-olide and 16-oxocleroda-3,13-dien-15-oic acid, quercetin, rutin, spinasterol, α-spinasterol, goniothalamin and (-)-5-hydroxygoniothalamin are the most potent anti-inflammatory compounds from Polyalthia species with comparable IC50 with positive controls.
CONCLUSIONS: Numerous pharmacological studies have supported the use of Polyalthia species against pain, rheumatic fever, haemorrhages and inflammation in traditional medicine. Flavonoids, diterpenoids, sterols and styrylpyrones from genus Polyalthia are the most significant class of compounds with potent anti-inflammatory activity. Secondary metabolites from these classes should be brought into further research to fill the gaps of knowledge in pharmacokinetics, pharmacodynamics, bioavailability, and toxicity in order to convert the pre-clinical results into clinical data for further investigation.

Matched MeSH terms: Biological Availability
Fulltext Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells

Nassir AM, Shahzad N, Ibrahim IAA, Ahmad I, Md S, Ain MR

Saudi Pharm J, 2018 Sep;26(6):876-885.
PMID: 30202231 DOI: 10.1016/j.jsps.2018.03.009

Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ± 1.49 and 41.1 ± 2.19 μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.

Matched MeSH terms: Biological Availability

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