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Formulation and Cost-Effectiveness of Fluid Gels as an Age-Appropriate Dosage Form for Older Adults with Dysphagia

Abd Aziz ZH, Katas H, Omar MS, Mohamed Shah N, Yusop SM

Dysphagia, 2021 Sep 13.
PMID: 34518932 DOI: 10.1007/s00455-021-10365-6

Dysphagia is associated with increased dependency and treatment costs, whereby patients resort to extemporaneous compounding that may further increase the number of adverse events and medical errors. In the management of dysphagia, increasing the bolus viscosity of medication such as fluid gels can be practiced. This study aimed to prepare and characterize the fluid gels as well as to estimate the cost of using fluid gels and compare it to the conventional practice of extemporaneous preparation of thickened liquid. Fluid gels were formulated using gellan gum and determined for physicochemical characteristics and in vitro drug release profile. The cost-based price of the fluid gel was estimated and compared to the cost of administering standard medication as well as administering thickened liquid using thickening powder. Fluid gels exhibited good physicochemical properties with the viscosity within nectar and honey consistency. A similar dissolution profile to the reference was observed for the 0.5% w/v gellan gum fluid gel and exhibiting the Higuchi release model. The price for 100 mL unit of 50 mg/mL paracetamol/acetaminophen and 20 mg/mL ibuprofen fluid gel was estimated to be about USD2.30 and USD2.37, respectively. A dose of 1000 mg paracetamol and 400 mg ibuprofen fluid gel was estimated to be about USD0.46 and USD0.47, respectively, which is lower than the cost of administering the same dose using extemporaneous thickened liquid. Fluid gels could be a cost-effective formulation for delivering medication in patients with dysphagia and can be developed on a profitable scale.
Antibacterial and Anti-Biofilm Biosynthesised Silver and Gold Nanoparticles for Medical Applications: Mechanism of Action, Toxicity and Current Status

Abdalla SSI, Katas H, Azmi F, Busra MFM

Curr Drug Deliv, 2020;17(2):88-100.
PMID: 31880259 DOI: 10.2174/1567201817666191227094334

Fast progress in nanoscience and nanotechnology has contributed to the way in which people diagnose, combat, and overcome various diseases differently from the conventional methods. Metal nanoparticles, mainly silver and gold nanoparticles (AgNPs and AuNPs, respectively), are currently developed for many applications in the medical and pharmaceutical area including as antibacterial, antibiofilm as well as anti-leshmanial agents, drug delivery systems, diagnostics tools, as well as being included in personal care products and cosmetics. In this review, the preparation of AgNPs and AuNPs using different methods is discussed, particularly the green or bio- synthesis method as well as common methods used for their physical and chemical characterization. In addition, the mechanisms of the antimicrobial and anti-biofilm activity of AgNPs and AuNPs are discussed, along with the toxicity of both nanoparticles. The review will provide insight into the potential of biosynthesized AgNPs and AuNPs as antimicrobial nanomaterial agents for future use.
Purification, characterization and comparative studies of spray-dried bacterial cellulose microparticles

Amin MC, Abadi AG, Katas H

Carbohydr Polym, 2014 Jan;99:180-9.
PMID: 24274495 DOI: 10.1016/j.carbpol.2013.08.041

Bacterial cellulose (BC) is a biopolymer with significant potential for the development of novel materials. This work aimed to prepare and characterize BC powders from nata de coco, and assess the possible enhancement of the powder properties by spray drying. Therefore, BC powders prepared by acid treatment and mechanical processing were spray-dried, and characterized according to their morphology, flowability, thermal stability, water retention capacity, and compared with commercial microcrystalline cellulose (MCC). The powders redispersibility and suspensions rheology were also evaluated. SEM showed that spray-dried BC microparticles exhibited semispherical shape and had flow rate of 4.23 g s(-1) compared with 0.52 g s(-1) for MCC. Particle size analysis demonstrated that spray-dried BC microparticles could be redispersed. TGA showed that BC samples had higher thermal stability than MCC. Water retention capacities of BC samples were greater than MCC. These findings provide new insight on the potential applications of spray-dried BC as a promising pharmaceutical excipient.
Fulltext Nanoscale Diblock copolymer micelles: characterizations and estimation of the effective diffusion coefficients of biomolecules release through cylindrical diffusion model

Amjad MW, Mohd Amin MC, Mahali SM, Katas H, Ismail I, Hassan MN, et al.

PLoS One, 2014;9(8):e105234.
PMID: 25133390 DOI: 10.1371/journal.pone.0105234

Biomolecules have been widely investigated as potential therapeutics for various diseases. However their use is limited due to rapid degradation and poor cellular uptake in vitro and in vivo. To address this issue, we synthesized a new nano-carrier system comprising of cholic acid-polyethylenimine (CA-PEI) copolymer micelles, via carbodiimide-mediated coupling for the efficient delivery of small interfering ribonucleic acid (siRNA) and bovine serum albumin (BSA) as model protein. The mean particle size of siRNA- or BSA-loaded CA-PEI micelles ranged from 100-150 nm, with zeta potentials of +3-+11 mV, respectively. Atomic force, transmission electron and field emission scanning electron microscopy demonstrated that the micelles exhibited excellent spherical morphology. No significant morphology or size changes were observed in the CA-PEI micelles after siRNA and BSA loading. CA-PEI micelles exhibited sustained release profile, the effective diffusion coefficients were successfully estimated using a mathematically-derived cylindrical diffusion model and the release data of siRNA and BSA closely fitted into this model. High siRNA and BSA binding and loading efficiencies (95% and 70%, respectively) were observed for CA-PEI micelles. Stability studies demonstrated that siRNA and BSA integrity was maintained after loading and release. The CA-PEI micelles were non cytotoxic to V79 and DLD-1 cells, as shown by alamarBlue and LIVE/DEAD cell viability assays. RT-PCR study revealed that siRNA-loaded CA-PEI micelles suppressed the mRNA for ABCB1 gene. These results revealed the promising potential of CA-PEI micelles as a stable, safe, and versatile nano-carrier for siRNA and the model protein delivery.
Fulltext Doxorubicin-loaded cholic acid-polyethyleneimine micelles for targeted delivery of antitumor drugs: synthesis, characterization, and evaluation of their in vitro cytotoxicity

Amjad MW, Amin MC, Katas H, Butt AM

Nanoscale Res Lett, 2012;7(1):687.
PMID: 23270381 DOI: 10.1186/1556-276X-7-687

Doxorubicin-loaded micelles were prepared from a copolymer comprising cholic acid (CA) and polyethyleneimine (PEI) for the delivery of antitumor drugs. The CA-PEI copolymer was synthesized via pairing mediated by N,N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide using dichloromethane as a solvent. Fourier transform infrared and nuclear magnetic resonance analyses were performed to verify the formation of an amide linkage between CA and PEI and doxorubicin localization into the copolymer. Dynamic light scattering and transmission electron microscopy studies revealed that the copolymer could self-assemble into micelles with a spherical morphology and an average diameter of <200 nm. The CA-PEI copolymer was also characterized by X-ray diffraction and differential scanning calorimetry. Doxorubicin-loaded micelles were prepared by dialysis method. A drug release study showed reduced drug release with escalating drug content. In a cytotoxicity assay using human colorectal adenocarcinoma (DLD-1) cells, the doxorubicin-loaded CA-PEI micelles exhibited better antitumor activity than that shown by doxorubicin. This is the first study on CA-PEI micelles as doxorubicin carriers, and this study demonstrated that they are promising candidates as carriers for sustained targeted antitumor drug delivery system.
In Vivo Antitumor Activity of Folate-Conjugated Cholic Acid-Polyethylenimine Micelles for the Codelivery of Doxorubicin and siRNA to Colorectal Adenocarcinomas

Amjad MW, Amin MC, Katas H, Butt AM, Kesharwani P, Iyer AK

Mol Pharm, 2015 Dec 7;12(12):4247-58.
PMID: 26567518 DOI: 10.1021/acs.molpharmaceut.5b00827

Multidrug resistance poses a great challenge to cancer treatment. In order to improve the targeting and codelivery of small interfering RNA (siRNA) and doxorubicin, and to overcome multidrug resistance, we conjugated a cholic acid-polyethylenimine polymer with folic acid, forming CA-PEI-FA micelles. CA-PEI-FA exhibited a low critical micelle concentration (80 μM), small average particle size (150 nm), and positive zeta potential (+ 12 mV). They showed high entrapment efficiency for doxorubicin (61.2 ± 1.7%, w/w), forming D-CA-PEI-FA, and for siRNA, forming D-CA-PEI-FA-S. X-ray photoelectron spectroscopic analysis revealed the presence of external FA on D-CA-PEI-FA micelles. About 25% doxorubicin was released within 24 h at pH 7.4, while more than 30% release was observed at pH 5. The presence of FA enhanced micelle antitumor activity. The D-CA-PEI-FA and D-CA-PEI-FA-S micelles inhibited tumor growth in vivo. No significant differences between their in vitro cytotoxic activities or their in vivo antitumor effects were observed, indicating that the siRNA coloading did not significantly increase the antitumor activity. Histological analysis revealed that tumor tissues from mice treated with D-CA-PEI-FA or D-CA-PEI-FA-S showed the lowest cancer cell density and the highest levels of apoptosis and necrosis. Similarly, the livers of these mice exhibited the lowest level of dihydropyrimidine dehydrogenase among all treated groups. The lowest serum vascular endothelial growth factor level (VEGF) (24.4 pg/mL) was observed in mice treated with D-CA-PEI-FA-S micelles using siRNA targeting VEGF. These findings indicated that the developed CA-PEI-FA nanoconjugate has the potential to achieve targeted codelivery of drugs and siRNA.
Preparation, characterization, and in vitro release studies of insulin-loaded double-walled poly(lactide-co-glycolide) microspheres

Ansary RH, Rahman MM, Awang MB, Katas H, Hadi H, Doolaanea AA

Drug Deliv Transl Res, 2016 06;6(3):308-18.
PMID: 26817478 DOI: 10.1007/s13346-016-0278-y

The purpose of this study was to fabricate insulin-loaded double-walled and single-polymer poly(lactide-co-glycolide) (PLGA) microspheres using a fast degrading glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu-PLGA), and a moderate degrading carboxyl-terminated PLGA polymers. A modified water-in-oil-in-oil-in-water (w/o/o/w) emulsion solvent evaporation technique was employed to prepare double-walled microspheres, whereas single-polymer microspheres were fabricated by a conventional water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The effect of fabrication techniques and polymer characteristics on microspheres size, morphology, encapsulation efficiency, in vitro release, and insulin stability was evaluated. The prepared double-walled microspheres were essentially non-porous, smooth surfaced, and spherical in shape, whereas single-polymer microspheres were highly porous. Double-walled microspheres exhibited a significantly reduced initial burst followed by sustained and almost complete release of insulin compared to single-polymer microspheres. Initial burst release was further suppressed from double-walled microspheres when the mass ratio of the component polymers was increased. In conclusion, double-walled microspheres made of Glu-PLGA and PLGA can be a potential delivery system of therapeutic insulin.
Preparation, characterization and in vitro release study of BSA-loaded double-walled glucose-poly(lactide-co-glycolide) microspheres

Ansary RH, Rahman MM, Awang MB, Katas H, Hadi H, Mohamed F, et al.

Arch Pharm Res, 2016 Sep;39(9):1242-56.
PMID: 26818028 DOI: 10.1007/s12272-016-0710-3

The aim of this study was to prepare a model protein, bovine serum albumin (BSA) loaded double-walled microspheres using a fast degrading glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu-PLGA) and a moderate-degrading carboxyl-terminated PLGA polymers to reduce the initial burst release and to eliminate the lag phase from the release profile of PLGA microspheres. The double-walled microspheres were prepared using a modified water-in-oil-in-oil-in-water (w/o/o/w) method and single-polymer microspheres were prepared using a conventional water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The particle size, morphology, encapsulation efficiency, thermal properties, in vitro drug release and structural integrity of BSA were evaluated in this study. Double-walled microspheres prepared with Glu-PLGA and PLGA polymers with a mass ratio of 1:1 were non-porous, smooth-surfaced, and spherical in shape. A significant reduction of initial burst release was achieved for the double-walled microspheres compared to single-polymer microspheres. In addition, microspheres prepared using Glu-PLGA and PLGA polymers in a mass ratio of 1:1 exhibited continuous BSA release after the small initial burst without any lag phase. It can be concluded that the double-walled microspheres made of Glu-PLGA and PLGA polymers in a mass ratio of 1:1 can be a potential delivery system for pharmaceutical proteins.
Fulltext Formulation and Evaluation of Microwave-Modified Chitosan-Curcumin Nanoparticles-A Promising Nanomaterials Platform for Skin Tissue Regeneration Applications Following Burn Wounds

Basit HM, Mohd Amin MCI, Ng SF, Katas H, Shah SU, Khan NR

Polymers (Basel), 2020 Nov 06;12(11).
PMID: 33171959 DOI: 10.3390/polym12112608

Improved physicochemical properties of chitosan-curcumin nanoparticulate carriers using microwave technology for skin burn wound application are reported. The microwave modified low molecular weight chitosan variant was used for nanoparticle formulation by ionic gelation method nanoparticles analyzed for their physicochemical properties. The antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa cultures, cytotoxicity and cell migration using human dermal fibroblasts-an adult cell line-were studied. The microwave modified chitosan variant had significantly reduced molecular weight, increased degree of deacetylation and decreased specific viscosity. The nanoparticles were nano-sized with high positive charge and good dispersibility with entrapment efficiency and drug content in between 99% and 100%, demonstrating almost no drug loss. Drug release was found to be sustained following Fickian the diffusion mechanism for drug release with higher cumulative drug release observed for formulation (F)2. The microwave treatment does not render a destructive effect on the chitosan molecule with the drug embedded in the core of nanoparticles. The optimized formulation precluded selected bacterial strain colonization, exerted no cytotoxic effect, and promoted cell migration within 24 h post application in comparison to blank and/or control application. Microwave modified low molecular weight chitosan-curcumin nanoparticles hold potential in delivery of curcumin into the skin to effectively treat skin manifestations.
Doxorubicin and siRNA Codelivery via Chitosan-Coated pH-Responsive Mixed Micellar Polyplexes for Enhanced Cancer Therapy in Multidrug-Resistant Tumors

Butt AM, Amin MC, Katas H, Abdul Murad NA, Jamal R, Kesharwani P

Mol Pharm, 2016 12 05;13(12):4179-4190.
PMID: 27934479

This study investigated the potential of chitosan-coated mixed micellar nanocarriers (polyplexes) for codelivery of siRNA and doxorubicin (DOX). DOX-loaded mixed micelles (serving as cores) were prepared by thin film hydration method and coated with chitosan (CS, serving as outer shell), and complexed with multidrug resistance (MDR) inhibiting siRNA. Selective targeting was achieved by folic acid conjugation. The polyplexes showed pH-responsive enhanced DOX release in acidic tumor pH, resulting in higher intracellular accumulation, which was further augmented by downregulation of mdr-1 gene after treatment with siRNA-complexed polyplexes. In vitro cytotoxicity assay demonstrated an enhanced cytotoxicity in native 4T1 and multidrug-resistant 4T1-mdr cell lines, compared to free DOX. Furthermore, in vivo, polyplexes codelivery resulted in highest DOX accumulation and significantly reduced the tumor volume in mice with 4T1 and 4T1-mdr tumors as compared to the free DOX groups, leading to improved survival times in mice. In conclusion, codelivery of siRNA and DOX via polyplexes has excellent potential as targeted drug nanocarriers for treatment of MDR cancers.
Fulltext Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

Butt AM, Mohd Amin MC, Katas H

Int J Nanomedicine, 2015;10:1321-34.
PMID: 25709451 DOI: 10.2147/IJN.S78438

BACKGROUND: Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells.
METHODS: FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue(®) assay.
RESULTS: The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX-DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX.
CONCLUSION: FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake.
Fulltext Antibacterial, Anti-Biofilm and Pro-Migratory Effects of Double Layered Hydrogels Packaged with Lactoferrin-DsiRNA-Silver Nanoparticles for Chronic Wound Therapy

Fathil MAM, Katas H

Pharmaceutics, 2023 Mar 19;15(3).
PMID: 36986852 DOI: 10.3390/pharmaceutics15030991

Antimicrobial resistance and biofilm formation in diabetic foot infections worsened during the COVID-19 pandemic, resulting in more severe infections and increased amputations. Therefore, this study aimed to develop a dressing that could effectively aid in the wound healing process and prevent bacterial infections by exerting both antibacterial and anti-biofilm effects. Silver nanoparticles (AgNPs) and lactoferrin (LTF) have been investigated as alternative antimicrobial and anti-biofilm agents, respectively, while dicer-substrate short interfering RNA (DsiRNA) has also been studied for its wound healing effect in diabetic wounds. In this study, AgNPs were complexed with LTF and DsiRNA via simple complexation before packaging in gelatin hydrogels. The formed hydrogels exhibited 1668% maximum swellability, with a 46.67 ± 10.33 µm average pore size. The hydrogels demonstrated positive antibacterial and anti-biofilm effects toward the selected Gram-positive and Gram-negative bacteria. The hydrogel containing AgLTF at 125 µg/mL was also non-cytotoxic on HaCaT cells for up to 72 h of incubation. The hydrogels containing DsiRNA and LTF demonstrated superior pro-migratory effects compared to the control group. In conclusion, the AgLTF-DsiRNA-loaded hydrogel possessed antibacterial, anti-biofilm, and pro-migratory activities. These findings provide a further understanding and knowledge on forming multipronged AgNPs consisting of DsiRNA and LTF for chronic wound therapy.
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.
Recent Advances in Polymer-based Wound Dressings for the Treatment of Diabetic Foot Ulcer: An Overview of State-of-the-art

Hussain Z, Thu HE, Shuid AN, Katas H, Hussain F

Curr Drug Targets, 2018;19(5):527-550.
PMID: 28676002 DOI: 10.2174/1389450118666170704132523

BACKGROUND: Diabetic foot ulcers (DFUs) are the chronic, non-healing complications of diabetic mellitus which compels a significant burden to the patients and the healthcare system. Peripheral vascular disease, diabetic neuropathy, and abnormal cellular and cytokine/chemokine activity are among the prime players which exacerbate the severity and prevent wound repair. Unlike acute wounds, DFUs impose a substantial challenge to the conventional wound dressings and demand the development of novel and advanced wound healing modalities. In general, an ideal wound dressing should provide a moist wound environment, offer protection from secondary infections, eliminate wound exudate and stimulate tissue regeneration.
OBJECTIVE: To date, numerous conventional wound dressings are employed for the management of DFUs but there is a lack of absolute and versatile choice. The current review was therefore aimed to summarize and critically discuss the available evidences related to pharmaceutical and therapeutic viability of polymer-based dressings for the treatment of DFUs.
RESULTS: A versatile range of naturally-originated polymers including chitosan (CS), hyaluronic acid (HA), cellulose, alginate, dextran, collagen, gelatin, elastin, fibrin and silk fibroin have been utilized for the treatment of DFUs. These polymers have been used in the form of hydrogels, films, hydrocolloids, foams, membranes, scaffolds, microparticles, and nanoparticles. Moreover, the wound healing viability and clinical applicability of various mutually modified, semi-synthetic or synthetic polymers have also been critically discussed.
CONCLUSION: In summary, this review enlightens the most recent developments in polymer-based wound dressings with special emphasis on advanced polymeric biomaterials, innovative therapeutic strategies and delivery approaches for the treatment of DFUs.
Efficient Colonic Delivery of DsiRNA by Pectin-Coated Polyelectrolyte Complex Nanoparticles: Preparation, Characterization and Improved Gastric Survivability

Hussain Z, Katas H, Yan SL, Jamaludin D

Curr Drug Deliv, 2017;14(7):1016-1027.
PMID: 28240178 DOI: 10.2174/1567201814666170224142446

BACKGROUND: Despite having excellent anticancer efficacy and ability to knockdown gene expression, the therapeutic feasibility of Dicer-substrate small interfering RNA (DsiRNA) is limited due to its poor cellular uptake, chemical instability and rapid degradation in biological environments.
OBJECTIVE: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA delivery to colon for the treatment of colorectal cancer.
METHOD: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA from gastric milieu.
RESULTS: The mean particle size and zeta potential of the prepared WSC-DsiRNA complexes were varied from 145 ± 4 nm to 867 ± 81 nm and +38 ± 4 to -6.2 ± 2.7 mV respectively, when the concentrations of WSC (0.1%, 0.2% and 0.3% w/v) and pectin (0.1%, 0.2% and 0.25% w/v) were varied. The electron microscopic analysis revealed that morphology of WSC-DsiRNA complexes was varied from smooth spherical to irregular spherical. Cytotoxicity analysis demonstrated that viability of colorectal adenocarcinoma cell was decreased when the dose of WSC-DsiRNA was increased over the incubation from 24 to 48 h. A significantly low cumulative release of DsiRNA in simulated gastric (<15%) and intestinal fluids (<30%) and a marked increase in its release (>90%) in simulated colonic fluid (SCF) evidenced the feasibility and suitability of WSC-DsiRNA complexes for the colonic delivery.
CONCLUSION: These findings clearly indicated promising potential of WSC-DsiRNA complexes as a carrier to delivery DsiRNA to colon for the treatment of colorectal cancer.
Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: A review of new trends and state-of-the-art

Hussain Z, Thu HE, Ng SF, Khan S, Katas H

Colloids Surf B Biointerfaces, 2017 Feb 01;150:223-241.
PMID: 27918967 DOI: 10.1016/j.colsurfb.2016.11.036

Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular structures, leading to restoration of the skin's barrier function, re-establishment of tissue integrity, and maintenance of the internal homeostasis. Curcumin (CUR) and its analogs have gained widespread recognition due to their remarkable anti-inflammatory, anti-infective, anticancer, immunomodulatory, antioxidant, and wound healing activities. However, their pharmaceutical significance is limited due to inherent hydrophobic nature, poor water solubility, low bioavailability, chemical instability, rapid metabolism and short half-life. Owing to their pharmaceutical limitations, newer strategies have been attempted in recent years aiming to mitigate problems related to the effective delivery of curcumanoids and to improve their wound healing potential. These advanced strategies include nanovesicles, polymeric micelles, conventional liposomes and hyalurosomes, nanocomposite hydrogels, electrospun nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, nanodispersion, and polymeric nanoparticles (NPs). The superior wound healing activities achieved after nanoencapsulation of the CUR are attributed to its target-specific delivery, longer retention at the target site, avoiding premature degradation of the encapsulated cargo and the therapeutic superiority of the advanced delivery systems over the conventional delivery. We have critically reviewed the literature and summarize the convincing evidence which explore the pharmaceutical significance and therapeutic feasibility of the advanced delivery systems in improving wound healing activities of the CUR and its analogs.
Fulltext Efficient immuno-modulation of TH1/TH2 biomarkers in 2,4-dinitrofluorobenzene-induced atopic dermatitis: nanocarrier-mediated transcutaneous co-delivery of anti-inflammatory and antioxidant drugs

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

PLoS One, 2014;9(11):e113143.
PMID: 25396426 DOI: 10.1371/journal.pone.0113143

The present study was conducted with the aim to investigate the immuno-modulatory and histological stabilization effects of nanocarrier-based transcutaneous co-delivery of hydrocortisone (HC) and hydroxytyrosol (HT). In this investigation, the clinical and pharmacological efficacies of nanoparticle (NP)-based formulation to alleviate 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) was explored by using an NC/Nga mouse model. Ex vivo visual examination of AD induction in experimental mice indicated remarkable control of NP-based formulations in reducing pathological severity of AD-like skin lesions. Therapeutic effectiveness of NP-based formulations was also evaluated by comparing skin thickness of AD-induced NP-treated mice (456±27 µm) with that of atopic mice (916±37 µm). Analysis of the immuno-spectrum of AD also revealed the dominance of NP-based formulations in restraining immunoglobulin-E (IgE), histamine, prostaglandin-E2 (PGE2), vascular endothelial growth factor-α (VEGF-α), and T-helper cells (TH1/TH2) producing cytokines in serum and skin biopsies of tested mice. These anti-AD data were further supported by histological findings that revealed alleviated pathological features, including collagen fiber deposition, fibroblasts infiltration, and fragmentation of elastic fibers in experimental mice. Thus, NP-mediated transcutaneous co-delivery of HC and HT can be considered as a promising therapy for managing immunological and histological spectra associated with AD.
Fulltext Antifungal activity of chitosan nanoparticles and correlation with their physical properties

Ing LY, Zin NM, Sarwar A, Katas H

Int J Biomater, 2012;2012:632698.
PMID: 22829829 DOI: 10.1155/2012/632698

The need of natural antimicrobials is paramount to avoid harmful synthetic chemicals. The study aimed to determine the antifungal activity of natural compound chitosan and its nanoparticles forms against Candida albicans, Fusarium solani and Aspergillus niger. Chitosan nanoparticles were prepared from low (LMW), high molecular weight (HMW) chitosan and its derivative, trimethyl chitosan (TMC). Particle size was increased when chitosan/TMC concentration was increased from 1 to 3 mg/mL. Their zeta potential ranged from +22 to +55 mV. Chitosan nanoparticles prepared from different concentrations of LMW and HMW were also found to serve a better inhibitory activity against C. albicans (MIC(LMW) = 0.25-0.86 mg/mL and MIC(HMW) = 0.6-1.0 mg/mL) and F. solani (MIC(LMW) = 0.86-1.2 mg/mL and MIC(HMW) = 0.5-1.2 mg/mL) compared to the solution form (MIC = 3 mg/mL for both MWs and species). This inhibitory effect was also influenced by particle size and zeta potential of chitosan nanoparticles. Besides, Aspergillus niger was found to be resistant to chitosan nanoparticles except for nanoparticles prepared from higher concentrations of HMW. Antifungal activity of nanoparticles prepared from TMC was negligible. The parent compound therefore could be formulated and applied as a natural antifungal agent into nanoparticles form to enhance its antifungal activity.

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