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Full circle: Resolving an adolescent's end-of-life issues

Abd Rahman FN, Lee VY, Shamsuddin AF, Yaakup H

Pediatr Int, 2015 Oct;57(5):1015-6.
PMID: 26286660 DOI: 10.1111/ped.12693

We report the challenges in managing a troubled, medically ill adolescent with end-of-life issues. Our role as multi-professional service providers complemented the family's efforts to help him reconcile with himself before death. The present experience enhances understanding of the biopsychosocial aspects of care. Every child has the right to optimal care.
Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment

Musa SH, Basri M, Masoumi HR, Karjiban RA, Malek EA, Basri H, et al.

Colloids Surf B Biointerfaces, 2013 Dec 1;112:113-9.
PMID: 23974000 DOI: 10.1016/j.colsurfb.2013.07.043

Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.
Fulltext Formulation optimization of a palm-based nanoemulsion system containing levodopa

Zainol S, Basri M, Basri HB, Shamsuddin AF, Abdul-Gani SS, Karjiban RA, et al.

Int J Mol Sci, 2012;13(10):13049-64.
PMID: 23202937 DOI: 10.3390/ijms131013049

Response surface methodology (RSM) was utilized to investigate the influence of the main emulsion composition; mixture of palm and medium-chain triglyceride (MCT) oil (6%-12% w/w), lecithin (1%-3% w/w), and Cremophor EL (0.5%-1.5% w/w) as well as the preparation method; addition rate (2-20 mL/min), on the physicochemical properties of palm-based nanoemulsions. The response variables were the three main emulsion properties; particle size, zeta potential and polydispersity index. Optimization of the four independent variables was carried out to obtain an optimum level palm-based nanoemulsion with desirable characteristics. The response surface analysis showed that the variation in the three responses could be depicted as a quadratic function of the main composition of the emulsion and the preparation method. The experimental data could be fitted sufficiently well into a second-order polynomial model. The optimized formulation was stable for six months at 4 °C.
Fulltext Resistance patterns of multidrug resistant Acinetobacter baumannii in an ICU of a tertiary care hospital, Malaysia

Janahiraman S, Aziz MN, Hoo FK, P'ng HS, Boo YL, Ramachandran V, et al.

Pak J Med Sci, 2015 Nov-Dec;31(6):1383-8.
PMID: 26870101 DOI: 10.12669/pjms.316.8445

Antimicrobial resistance is a major health problem worldwide in hospitals. The main contributing factors are exposures to broad-spectrum antimicrobials and cross-infections. Understanding the extent and type of antimicrobial use in tertiary care hospitals will aid in developing national antimicrobial stewardship priorities.
Fulltext Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics

Harun SN, Nordin SA, Gani SSA, Shamsuddin AF, Basri M, Basri HB

Int J Nanomedicine, 2018;13:2571-2584.
PMID: 29731632 DOI: 10.2147/IJN.S151788

Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood-brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.
Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.
Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0-
t
, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0-
t
, prolonged half-life, and lower clearance as compared to free cefuroxime solution.
Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.
Fulltext A new alternative for intravenous lipid emulsion 20% w/w from superolein oil and its effect on lipid and liver profiles in an animal model

Amran MHH, Zulfakar MH, Danik MF, Abdullah MSP, Shamsuddin AF

Daru, 2019 Jun;27(1):191-201.
PMID: 31020546 DOI: 10.1007/s40199-019-00262-7

PURPOSE: Intravenous lipid emulsion (IVLE) was first used to prevent essential fatty acids deficiency. IVLE with α-tocopherol was reported to provide protection against parenteral nutrition-associated liver disease. This study aims to determine the optimal parameters and conditions in developing a physically stable IVLE from superolein palm oil (SoLE 20%) and its effect on lipid and liver profiles in an animal model.
METHODS: SoLE 20% was prepared using superolein oil and MCT oil (1:1), stabilized with egg lecithin and homogenized using a high pressure homogenizer. Mean droplet size was used as the response variable and was measured using laser diffraction and dynamic light scattering method. Physical stability at 4 °C, 25 °C and 40 °C storage temperatures were determined based on particle size and distribution, polydispersity index, zeta potential, viscosity, vitamin E contents and pH. Sterility and pyrogenicity were also investigated. Rabbits were administered with 1.0 g/kg SoLE 20% for 5 h and repeated daily for 3 days to investigate its effect on blood lipid and liver enzymes profile.
RESULTS: SoLE 20% was succesfully prepared using the optimized parameters of 800 psi, 7 cycles and 1.2 g lecithin. The IVLE prepared had a particle size of 252.60 ± 4.88 nm and was physically stable for 4 weeks at different storage temperatures. SoLE 20% had a high content of natural vitamin E, remained sterile and pyrogen free. It was also safe for intravenous administration and did not alter the blood lipid (p > 0.05) and liver enzymes profiles (p > 0.05) of the rabbits.
CONCLUSION: The optimal parameters to develop a stable superolein based IVLE are 800 psi homogenization pressure, 7 homogenization cycles and using 1.2 g lecithin as the emulsifier. SoLE 20% is safe for intravenous administration and does not significantly alter lipid and liver enzymes profiles of the rabbits.
Fulltext Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir

Hassan H, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, Basir R

Molecules, 2021 Sep 07;26(18).
PMID: 34576904 DOI: 10.3390/molecules26185432

Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.
Fulltext Acyclovir-Loaded Solid Lipid Nanoparticles: Optimization, Characterization and Evaluation of Its Pharmacokinetic Profile

Hassan H, Bello RO, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, et al.

Nanomaterials (Basel), 2020 Sep 09;10(9).
PMID: 32916823 DOI: 10.3390/nano10091785

Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of acyclovir-loaded SLNs was four-fold higher than the commercial suspension. Thus, this investigation presented promising results that the method developed for encapsulation of acyclovir offers potential as an alternative pathway to enhance the drug's bioavailability. In conclusion, this study exhibited the feasibility of SLNs as an oral delivery vehicle for acyclovir and therefore represents a new promising therapeutic concept of acyclovir treatment via a nanoparticulate drug delivery system.