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Fulltext Synthesis, characterisation, and evaluation of a cross-linked disulphide amide-anhydride-containing polymer based on cysteine for colonic drug delivery

Lim V, Peh KK, Sahudin S

Int J Mol Sci, 2013;14(12):24670-91.
PMID: 24351841 DOI: 10.3390/ijms141224670

The use of disulphide polymers, a low redox potential responsive delivery, is one strategy for targeting drugs to the colon so that they are specifically released there. The objective of this study was to synthesise a new cross-linked disulphide-containing polymer based on the amino acid cysteine as a colon drug delivery system and to evaluate the efficiency of the polymers for colon targeted drug delivery under the condition of a low redox potential. The disulphide cross-linked polymers were synthesised via air oxidation of 1,2-ethanedithiol and 3-mercapto-N-2-(3-mercaptopropionamide)-3-mercapto propionic anhydride (trithiol monomers) using different ratio combinations. Four types of polymers were synthesised: P10, P11, P151, and P15. All compounds synthesised were characterised by NMR, IR, LC-MS, CHNS analysis, Raman spectrometry, SEM-EDX, and elemental mapping. The synthesised polymers were evaluated in chemical reduction studies that were performed in zinc/acetic acid solution. The suitability of each polymer for use in colon-targeted drug delivery was investigated in vitro using simulated conditions. Chemical reduction studies showed that all polymers were reduced after 0.5-1.0 h, but different polymers had different thiol concentrations. The bacterial degradation studies showed that the polymers were biodegraded in the anaerobic colonic bacterial medium. Degradation was most pronounced for polymer P15. This result complements the general consensus that biodegradability depends on the swellability of polymers in an aqueous environment. Overall, these results suggest that the cross-linked disulphide-containing polymers described herein could be used as coatings for drugs delivered to the colon.
Polymeric nanoparticles for topical delivery of alpha and beta arbutin: preparation and characterization

Ayumi NS, Sahudin S, Hussain Z, Hussain M, Samah NHA

Drug Deliv Transl Res, 2019 04;9(2):482-496.
PMID: 29569027 DOI: 10.1007/s13346-018-0508-6

To investigate the use of chitosan nanoparticles (CS-TPP-NPs) as carriers for α- and β-arbutin. In this study, CS-TPP-NPs containing α- and β-arbutin were prepared via the ionic cross-linking of CS and TPP and characterized for particle size, zeta potential, and dispersity index. The entrapment efficiency and loading capacity of various β-arbutin concentrations (0.1, 0.2, 0.4, 0.5, and 0.6%) were also investigated. SEM, TEM FTIR, DSC and TGA analyses of the nanoparticles were performed to further characterize the nanoparticles. Finally, stability and release studies were undertaken to ascertain further the suitability of the nanoparticles as a carrier system for α- and β-arbutin. Data obtained clearly indicates the potential for use of CS-TPP-NPs as a carrier for the delivery of α- and β-arbutin. The size obtained for the alpha nanoparticles (α-arbutin CSNPs) ranges from 147 to 274 d.nm, with an increase in size with increasing alpha arbutin concentration. β-arbutin nanoparticles (β-arbutin CSNPs) size range was from 211.1 to 284 dn.m. PdI for all nanoparticles remained between 0.2-0.3 while the zeta potential was between 41.6-52.1 mV. The optimum encapsulation efficiency and loading capacity for 0.4% α-arbutin CSNPs were 71 and 77%, respectively. As for β-arbutin, CSNP optimum encapsulation efficiency and loading capacity for 0.4% concentration were 68 and 74%, respectively. Scanning electron microscopy for α-arbutin CSNPs showed a more spherical shape compared to β-arbutin CSNPs where rod-shaped particles were observed. However, under transmission electron microscopy, the shapes of both α- and β-arbutin CSNP nanoparticles were spherical. The crystal phase identification of the studied samples was carried out using X-ray diffraction (XRD), and the XRD of both α and β-arbutin CSNPs showed to be more crystalline in comparison to their free form. FTIR spectra showed intense characteristic peaks of chitosan appearing at 3438.3 cm-1 (-OH stretching), 2912 cm-1 (-CH stretching), represented 1598.01 cm-1 (-NH2) for both nanoparticles. Stability studies conducted for 90 days revealed that both α- and β-arbutin CSNPs were stable in solution. Finally, release studies of both α- and β-arbutin CSNPs showed a significantly higher percentage release in comparison to α- and β-arbutin in their free form. Chitosan nanoparticles demonstrate considerable promise as a carrier system for α- and β-arbutin, the use of which is anticipated to improve delivery of arbutin through the skin, in order to improve its efficacy as a whitening agent.
Chitosan-Based Nanocarriers for Pulmonary and Intranasal Drug Delivery Systems: A Comprehensive Overview of their Applications

Alwahsh W, Sahudin S, Alkhatib H, Bostanudin MF, Alwahsh M

Curr Drug Targets, 2024 Apr 26.
PMID: 38676513 DOI: 10.2174/0113894501301747240417103321

The optimization of respiratory health is important, and one avenue for achieving this is through the application of both Pulmonary Drug Delivery System (PDDS) and Intranasal Delivery (IND). PDDS offers immediate delivery of medication to the respiratory system, providing advantages, such as sustained regional drug concentration, tunable drug release, extended duration of action, and enhanced patient compliance. IND, renowned for its non-invasive nature and swift onset of action, presents a promising path for advancement. Modern PDDS and IND utilize various polymers, among which Chitosan (CS) stands out. CS is a biocompatible and biodegradable polysaccharide with unique physicochemical properties, making it well-suited for medical and pharmaceutical applications. The multiple positively charged amino groups present in CS facilitate its interaction with negatively charged mucous membranes, allowing CS to adsorb easily onto the mucosal surface. In addition, CS-based nanocarriers have been an important topic of research. Polymeric Nanoparticles (NPs), liposomes, dendrimers, microspheres, nanoemulsions, Solid Lipid Nanoparticles (SLNs), carbon nanotubes, and modified effective targeting systems compete as important ways of increasing pulmonary drug delivery with chitosan. This review covers the latest findings on CS-based nanocarriers and their applications.
Fulltext Students perception of an industry based approach problem based learning (PBL) and their performance in drug delivery courses

Hussain M, Sahudin S, Abu Samah NH, Anuar NK

Saudi Pharm J, 2019 Feb;27(2):274-282.
PMID: 30766440 DOI: 10.1016/j.jsps.2018.11.009

OBJECTIVE: To investigate students perception of an industry based approach problem based learning (PBL) and their performance in drug delivery courses in pharmaceutics.
METHODS: PBL was implemented within two drug delivery courses in 2015, in anticipation that the use of formulation or industrial instead of clinical or pharmacy practice based triggers, would open up student interest and understanding towards learning pharmaceutics in relation to industrial pharmacy. Two cohorts were monitored through final year examination results and PBL feedback to evaluate student perception and acceptance of the use of PBL. Previous cohorts were only exposed to conventional tutorials.
RESULTS: Both cohorts showed better performance in their final examination results (2015 & 2016) compared to the previous year (2014) when students were only exposed to tutorials. The maximum and average marks obtained were also higher. There was significant difference between the maximum marks for Drug Delivery Systems 2 and the average marks for Drug Delivery Systems 1 with P 
Fulltext Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles

Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E, Sahudin S

Int J Nanomedicine, 2014;9:5143-56.
PMID: 25395851 DOI: 10.2147/IJN.S71543

Atopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC).
Antidermatitic perspective of hydrocortisone as chitosan nanocarriers: an ex vivo and in vivo assessment using an NC/Nga mouse model

Hussain Z, Katas H, Amin MC, Kumulosasi E, Sahudin S

J Pharm Sci, 2013 Mar;102(3):1063-75.
PMID: 23303620 DOI: 10.1002/jps.23446

The aim of this study to administer hydrocortisone (HC) percutaneously in the form of polymeric nanoparticles (NPs) to alleviate its transcutaneous absorption, and to derive additional wound-healing benefits of chitosan. HC-loaded NPs had varied particle sizes, zeta potentials, and entrapment efficiencies, when drug-to-polymer mass ratios increased from 1:1 to 1:8. Ex vivo permeation analysis showed that the nanoparticulate formulation of HC significantly reduced corresponding flux [∼24 µg/(cm(2) h)] and permeation coefficient (∼4.8 × 10(-3) cm/h) of HC across the full thickness NC/Nga mouse skin. The nanoparticulate formulation also exhibited a higher epidermal (1610 ± 42 µg/g of skin) and dermal (910 ± 46 µg/g of skin) accumulation of HC than those associated with control groups. An in vivo assessment using an NC/Nga mouse model further revealed that mice treated with the nanoparticulate system efficiently controlled transepidermal water loss [15 ± 2 g/(m(2) h)], erythema intensity (232 ± 12), dermatitis index (mild), and thickness of skin (456 ± 27 µm). Taken together, histopathological examination predicted that the nanoparticulate system showed a proficient anti-inflammatory and antifibrotic activity against atopic dermatitic (AD) lesions. Our results strongly suggest that HC-loaded NPs have promising potential for topical/transdermal delivery of glucocorticoids in the treatment of AD.
Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model

Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E, Buang F, Sahudin S

Int J Pharm, 2013 Feb 28;444(1-2):109-19.
PMID: 23337632 DOI: 10.1016/j.ijpharm.2013.01.024

In this study, hydroxytyrosol (HT; a potent antioxidant) was co-administered with hydrocortisone (HC) to mitigate the systemic adverse effects of the latter and to provide additional anti-inflammatory and antioxidant benefits in the treatment of atopic dermatitis (AD). The co-loaded nanoparticles (NPs) prepared had shown different particle sizes, zeta potentials, loading efficiencies, and morphology, when the pH of the chitosan solution was increased from 3.0 to 7.0. Ex vivo permeation data showed that the co-loaded NPs formulation significantly reduced the corresponding flux (17.04μg/cm(2)/h) and permeation coefficient (3.4×10(-3)cm/h) of HC across full-thickness NC/Nga mouse skin. In addition, the NPs formulation showed higher epidermal (1560±31μg/g of skin) and dermal (880±28μg/g of skin) accumulation of HC than did a commercial HC formulation. Moreover, an in vivo study using an NC/Nga mouse model revealed that compared to the other treatment groups, the group treated with the NPs formulation efficiently controlled transepidermal water loss (13±2g/m(2)/h), intensity of erythema (207±12), and dermatitis index (mild). In conclusion, NPs co-loaded with HC/HT is proposed as a promising system for the percutaneous co-delivery of anti-inflammatory and antioxidative agents in the treatment of AD.
Formulation and In-Vitro Characterisation of Cross-Linked Amphiphilic Guar Gum Nanocarriers for Percutaneous Delivery of Arbutin

Bostanudin MF, Salam A, Mahmood A, Arafat M, Kaharudin AN, Sahudin S, et al.

J Pharm Sci, 2021 Dec;110(12):3907-3918.
PMID: 34403653 DOI: 10.1016/j.xphs.2021.08.014

Nano-colloidal systems formulated from amphiphilically-modified polysaccharides (degree of modification 16.6%) are focus of prominent study due to their potential to augment active penetration across the skin. Here we report the synthesis of amphiphilically-modified guar gum (GBE-GG) prepared by grafting with glycidol butyl ether (GBE), which were subsequently formed into nanocarriers and loaded with α-arbutin (22.3% loading). The monodispersed and close-to-spherical nanocarriers (size range 239-297 nm) formed via cross-linking were adequately stable mainly at low temperature (4 °C) under physiological pH condition. α-arbutin was released from GBE-GG NPs in a more sustained manner and the release profiles can be accurately represented by the 1st order kinetic model. In-vitro interactions on immortalised human keratinocytes (HaCaT) cells revealed an increase in biological membrane permeability as well as the absence of cellular toxicity at application pertinent concentrations. No substantial haemolytic activity appeared and flow cytometry analysis revealed effective cellular uptake, suggesting their potential as promising nanocarriers for percutaneous delivery that warrants further comprehensive research.
Self-assembled chitosan-insulin oral nanoparticles - A critical perspective review

Chellathurai MS, Yong CL, Sofian ZM, Sahudin S, Hasim NBM, Mahmood S

Int J Biol Macromol, 2023 Jul 15;243:125125.
PMID: 37263321 DOI: 10.1016/j.ijbiomac.2023.125125

Chitosan is an abundant natural cationic polysaccharide with excellent biodegradability, bioadhesion, and biocompatibility. Chitosan is extensively researched for various particulate oral insulin drug delivery systems. Oral insulin is economically efficient and more convenient than injections, with greater patient compliance. Electrostatic ionic interaction between cationic chitosan and anionic polymer or insulin leads to the formation of spontaneously self-assembled nanoparticles. This simple technique attracted many researchers as it can be carried out quickly in mild conditions without harmful solvents, such as surfactants or chemical cross-linkers that might degrade the insulin structure. The formulated chitosan nanoparticles help to protect the core insulin from enzymatic degradation in the digestive system and improve paracellular intestinal uptake from the enterocytes due to mucoadhesion and reversible tight junction opening. Moreover, functionalized chitosan nanoparticles create newer avenues for targeted and prolonged delivery. This review focuses on modified chitosan-insulin nanoparticles and their implications on oral insulin delivery. Dependent variables and their optimal concentration ranges used in self-assembly techniques for chitosan-insulin nanoparticular synthesis are summarized. This review provides a comprehensive guide to fine-tune the essential factors to formulate stable insulin-chitosan nanoparticles using mild ionic interactions.
Fulltext The use of herbal and dietary supplement among community-dwelling elderly in a suburban town of Malaysia

Wahab MSA, Zaini MH, Ali AA, Sahudin S, Mehat MZ, Hamid HA, et al.

BMC Complement Med Ther, 2021 Apr 01;21(1):110.
PMID: 33794868 DOI: 10.1186/s12906-021-03287-1

BACKGROUND: The use of herbal and dietary supplement (HDS) in health and disease management has gained global attention. HDS are generally accepted by the public and are associated with positive health behaviours. However, several reports have been documented with regards to their potential adverse effects and interaction with conventional medicines. Limited data is currently available on the use of HDS among elderly population in Malaysia. This present study aims to investigate the prevalence of and pattern of HDS use among a sample of community-dwelling elderly in a suburban town in Malaysia.
METHODS: A cross-sectional survey was conducted between March and May 2019 among the elderly aged ≥60 years old. The participants with the following criteria were included in the study: aged ≥60 years, residing in Puncak Alam and able to understand Malay or English language. Data were collected using a pre-validated questionnaire. All statistical analysis was conducted using IBM SPSS ver. 23.
RESULTS: Overall, 336 out of 400 elderly responded to the survey, achieving a response rate of 84%. This study observed that almost 50% of the respondents were using at least one type of HDS in the past one month of the survey. Among HDS non-users, most of them preferred to use modern medicines (62.6%, 114/182). Among the HDS users, 75.3% (116/154) were using at least one type of modern medicine (prescription or over-the-counter medicine). Multivariate analysis showed that having good to excellent perceived health (adjusted OR = 2.666, 95% CI = 1.592-4.464), having felt sick at least once in the past one month (adjusted OR = 2.500, 95% CI = 1.426-4.383), and lower body mass index (adjusted OR = 0.937, 95% CI = 0.887-0.990) were associated with HDS use. It was noted that only a small percentage of HDS users (16.2%, 25/154) had informed healthcare providers on their HDS use.
CONCLUSION: The use of HDS is common among the elderly sampled. Hence, healthcare providers should be more vigilant in seeking information of HDS use for disease management in their elderly patients. Campaigns that provide accurate information regarding the appropriate use of HDS among the elderly are pertinent to prevent misinformation of the products.

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