Shariza Sahudin

Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model.

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.

Antidermatitic perspective of hydrocortisone as chitosan nanocarriers: An ex vivo and in vivo assessment using an NC/Nga mouse model

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.

Synthesis of a new potential conjugated TAT-peptide-chitosan nanoparticles carrier via disulphide linkage

Chitosan and TAT peptide have been widely investigated as delivery systems for various biomolecules such as plasmid DNA, oligonucleotides, and siRNAs. Conjugation of chitosan with TAT-peptide was therefore expected to produce a carrier with enhanced ability to facilitate cellular uptake. In this study, chitosan nanoparticles (CNs) were prepared by ionic gelation method prior to conjugation with TAT-peptide via disulphide linkage (CN-TAT). The conjugation was performed at various TAT-peptideto-chitosan weight ratios ranging from 0.008 : 1 to 0.125 : 1. siRNA as a model biomolecule was loaded by adsorption onto the CN-TAT. Nanosize range particles were produced with a size range of less than 700nm depending on TAT-peptide concentration used. HPLC and Raman spectrometry analysis revealed that TAT-peptide was successfully conjugated to the CN via disulphide linkage. siRNA loading efficiency for CN-TAT was 93% ±0.01. In vitro cytotoxicity studies showed that CN-TAT has relatively low toxicity. In conclusion, TAT conjugated onto CN via disulphide linkage was successfully synthesized, and its low cytoxicity demonstrates a potential for its use as a vector for biomolecules.

Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles

Background 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). Methods In this study, HC, the least potent topical glucocorticoid, was administered transcutaneously as chitosan NPs. The pharmacological and immunological effects of the NP-based HC delivery on the alleviation of 2,4-dinitrofluorobenzene-induced atopic dermatitis (AD)-like skin lesions were evaluated using the NC/Nga mouse model. Results In vivo Dino-Lite® microscopic assessment revealed that the NP-based formulation displayed a remarkable ability to reduce the severity of the pathological features of AD (dermatitis index, 3.0). The AD suppressive activity of the NP-based topical formulation was expected owing to the interruption of a series of immunopathological events, including the production of immunoglobulin E, release of histamine, and expression of prostaglandin-E2 and vascular endothelial growth factor-α in the sera and skin of the tested animals. Analysis of the cytokine expression in AD-like skin lesions further revealed that the NP-based formulation inhibited the pathological expression of interleukin (IL)-4, IL-5, IL-6, IL-13, IL-12p70, interferon-γ, and tumor necrosis factor-α in serum and skin homogenates of NC/Nga mice. Further, our histological findings indicated that the NP-based formulation inhibited fibroblast infiltration and fragmentation of elastic fibers, further supporting the clinical importance of these formulations in maintaining the integrity of elastic connective tissues. Conclusion The current investigation suggests that NP-mediated transcutaneous delivery of HC could be considered an effective therapeutic approach to manage dermatitis.

Synthesis, Characterisation, and Evaluation of a Cross-Linked Disulphide Amide-Anhydride-Containing Polymer Based on Cysteine for Colonic Drug Delivery

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.

A preliminary study of the potential role of Malaysian community pharmacists in type 2 diabetes medicines management clinics

A substantial proportion of Malaysians with type 2 diabetes do not take medication as prescribed and despite the availability of diabetes medication therapy adherence clinics services within government hospitals, many patients do not benefit. Community pharmacists are in an ideal position to play an important role in providing adherence clinics within primary care.

A Diabetes and Obesity Crisis: Preliminary Study of Lifestyle, Diet, Knowledge and Attitude of Malaysian Pharmacy Undergraduates Towards Type-2 Diabetes

Background : Patient education and self-care are important not only for diabetes prevention but also chronic disease management. Community pharmacists are an ideal position to play a role in providing medicines management, lifestyle and preventative advice specific to type-2 diabetes care, Malaysian pharmacists must be ready and willing to firmly establish such clear roles and as such, undergraduate pharmacy students need to be equipped with the skills and mind-set to accept such a challenge Objective : To explore knowledge and awareness of pharmacy undergraduate students at Universiti Technology MARA (UiTM) towards diabetes risk factors. To identify potential diabetes risk factors by evaluating dietary intake and to determine students’ attitude towards their future roles as health care providers. Method : 159 Malaysian third-year undergraduate pharmacy students were provided a questionnaire and a two-day food diary. The questionnaire consisted of four sections to examine demographics, lifestyle and diet, together with knowledge of diabetes and the perception of pharmacists’ role. Results : A total of 113 completed questionnaires were received. 20% of the respondents were overweight or obese and 21% had elevated blood pressure. 95% of students consumed only 50% of the recommend daily calorie intake for adults. Students however possessed good knowledge of diabetes with a positive attitude towards pharmacist roles in healthcare. Conclusion : Overall, the health status of Malaysian pharmacy students is very similar to the general population, displaying similar risk factors and dietary habits despite their status as future healthcare professionals. Students do however display a good knowledge of diabetes and appear positive towards their roles as future pharmacists.