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Topical application of omega-3-, omega-6-, and omega-9-rich oil emulsions for cutaneous wound healing in rats

Ishak WMW, Katas H, Yuen NP, Abdullah MA, Zulfakar MH

Drug Deliv Transl Res, 2019 04;9(2):418-433.
PMID: 29667150 DOI: 10.1007/s13346-018-0522-8

Wound healing is a physiological event that generates reconstitution and restoration of granulation tissue that ends with scar formation. As omega fatty acids are part of membrane phospholipids and participate in the inflammatory response, we investigated the effects of omega-3, omega-6, and omega-9 fatty acids in the form of oils on wound healing. Linseed (LO), evening primrose (EPO), and olive oils (OO) rich in omega-3, omega-6, and omega-9 fatty acids were formulated into emulsions and were topically applied on rats with excision wounds. All omega-3-, omega-6-, and omega-9-rich oil formulations were found to accelerate wound closure compared to untreated, with significant improvement (p
Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release

Katas H, Wen CY, Siddique MI, Hussain Z, Mohd Fadhil FH

Ther Deliv, 2017 01;8(3):137-150.
PMID: 28145827 DOI: 10.4155/tde-2016-0075

AIM: Chitosan (CS) has been extensively studied as drug delivery systems for wound healing. Results/methodology: CS nanoparticles were loaded with curcumin (Cur) and DsiRNA against prostaglandin transporter gene and they were incorporated into 20 and 25% w/v Pluronic F-127. The gels were later analyzed for their rheology, gelation temperature (Tgel), morphology, drug incorporation and in vitro drug release. The particle size was in the range of 231 ± 17-320 ± 20 nm, depending on CS concentration. The gels had Tgel of 23-28°C and exhibited sustained drug release with high accumulated amount of drugs over 48 h.
CONCLUSION: A thermo-sensitive gel containing Cur/DsiRNA CS nanoparticles was successfully developed and has a great potential to be further developed.
Fulltext Therapeutic Approach of Flavonoid in Ameliorating Diabetic Cardiomyopathy by Targeting Mitochondrial-Induced Oxidative Stress

Sapian S, Taib IS, Latip J, Katas H, Chin KY, Mohd Nor NA, et al.

Int J Mol Sci, 2021 Oct 27;22(21).
PMID: 34769045 DOI: 10.3390/ijms222111616

Diabetes cardiomyopathy is one of the key factors of mortality among diabetic patients around the globe. One of the prior contributors to the progression of diabetic cardiomyopathy is cardiac mitochondrial dysfunction. The cardiac mitochondrial dysfunction can induce oxidative stress in cardiomyocytes and was found to be the cause of majority of the heart morphological and dynamical changes in diabetic cardiomyopathy. To slow down the occurrence of diabetic cardiomyopathy, it is crucial to discover therapeutic agents that target mitochondrial-induced oxidative stress. Flavonoid is a plentiful phytochemical in plants that shows a wide range of biological actions against human diseases. Flavonoids have been extensively documented for their ability to protect the heart from diabetic cardiomyopathy. Flavonoids' ability to alleviate diabetic cardiomyopathy is primarily attributed to their antioxidant properties. In this review, we present the mechanisms involved in flavonoid therapies in ameliorating mitochondrial-induced oxidative stress in diabetic cardiomyopathy.
Fulltext The Role of Anthocyanin in Modulating Diabetic Cardiovascular Disease and Its Potential to Be Developed as a Nutraceutical

Sapian S, Taib IS, Katas H, Latip J, Zainalabidin S, Hamid ZA, et al.

Pharmaceuticals (Basel), 2022 Oct 30;15(11).
PMID: 36355516 DOI: 10.3390/ph15111344

Cardiovascular disease (CVD) is directly linked to diabetes mellitus (DM), and its morbidity and mortality are rising at an alarming rate. Individuals with DM experience significantly worse clinical outcomes due to heart failure as a CVD consequence than non-diabetic patients. Hyperglycemia is the main culprit that triggers the activation of oxidative damage, inflammation, fibrosis, and apoptosis pathways that aggravate diabetic CVD progression. In recent years, the development of phytochemical-based nutraceutical products for diabetic treatment has risen due to their therapeutic properties. Anthocyanin, which can be found in various types of plants, has been proposed for preventing and treating various diseases, and has elicited excellent antioxidative, anti-inflammation, anti-fibrosis, and anti-apoptosis effects. In preclinical and clinical studies, plants rich in anthocyanin have been reported to attenuate diabetic CVD. Therefore, the development of anthocyanin as a nutraceutical in managing diabetic CVD is in demand. In this review, we unveil the role of anthocyanin in modulating diabetic CVD, and its potential to be developed as a nutraceutical for a therapeutic strategy in managing CVD associated with DM.
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 Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers

Raja MA, Katas H, Jing Wen T

PLoS One, 2015;10(6):e0128963.
PMID: 26068222 DOI: 10.1371/journal.pone.0128963

Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting.
Simvastatin nanoparticles loaded polymeric film as a potential strategy for diabetic wound healing: in vitro and in vivo evaluation

Tufail S, Siddique MI, Sarfraz M, Sohail MF, Shahid MN, Omer MO, et al.

Curr Drug Deliv, 2021 Jul 20.
PMID: 34288836 DOI: 10.2174/1567201818666210720150929

INTRODUCTION: The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds.
AIM: Aim of the present study is to fabricate nanofilm embedded with simvastatin loaded chitosan nanoparticles (CS-SIM-NPs) has been reported herein to explore the efficacy of SIM in diabetic wound healing.
METHODS: The NPs, prepared via ionic gelation, were 173nm ± 2.645 in size with a zeta potential -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats.
RESULTS: The results showed significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site.
CONCLUSION: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.
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.
Fulltext Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

Sarwar A, Katas H, Samsudin SN, Zin NM

PLoS One, 2015;10(4):e0123084.
PMID: 25928293 DOI: 10.1371/journal.pone.0123084

Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future medical applications. Chitosan derivatives with triazole functionality, synthesized by Huisgen 1,3-dipolar cycloaddition, and their nanoparticles showed significant enhancement in antibacterial and antifungal activities in comparison to those associated with native, non-altered chitosan.
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.
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.
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 Preparation and characterisation of highly loaded fluorescent chitosan nanoparticles

Katas H, Mui Wen C

ISRN Pharm, 2011;2011:246162.
PMID: 22389847 DOI: 10.5402/2011/246162

Chitosan (CS) nanoparticles have been developed as a versatile drug delivery system to transport drugs, genes, proteins, and peptides into target sites. Demands on fluorescent nanoparticles have increased recently due to various applications in medical and stem-cell-based researches. In this study, fluorescent CS nanoparticles were prepared by a mild method, namely, complex coacervation. Entrapment efficiency of sulforhodamine (SR101) loaded into CS nanoparticles was investigated to evaluate their capacity in incorporating fluorescent molecule. Particle size of produced fluorescent nanoparticles was in the range of 600-700 nm, and their particle size was highly dependent on the CS molecular weight as well as concentration. A high entrapment efficiency of SR101 into CS nanoparticles could also be obtained when it was dissolved in methanol. In conclusion, highly loaded fluorescent CS nanoparticles could be easily prepared using complex coacervation method and therefore can be applied in various medical researches.
Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects

Siddique MI, Katas H, Jamil A, Mohd Amin MCI, Ng SF, Zulfakar MH, et al.

Drug Deliv Transl Res, 2019 04;9(2):469-481.
PMID: 29159691 DOI: 10.1007/s13346-017-0439-7

Hydrocortisone (HC), topical glucocorticoid along with hydroxytyrosol (HT), and anti-microbial- and anti-oxidant-loaded chitosan nanoparticles (CSNPs) were prepared in large scale and analyzed for their adverse effects on healthy human skin followed by repeated applications. Ten subjects were randomized to receive test (HC-HT CSNPs) and vehicle samples (aqueous (AQ) cream). They were applied on the arms for 28 days, and transepidermal water loss (TEWL), erythema intensity, and irritation score were measured. Blood samples were analyzed for blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone (ACTH) levels. Skin biopsy was obtained to assess histopathological changes in the skin. HC-HT CSNP AQ cream was stored at 4, 25, and 45 °C for a period of 1 year, and its stability was assessed by monitoring their physical appearances, particle size, and pH. Spherical-shaped NPs were successfully upscaled using spinning-disc technology, with insignificant changes in particle size, zeta potential, and incorporation of drugs as compared to the well-established laboratory method. Particle size of HC-HT CSNPs was H&E) staining results. Comparative results of blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone level at day 0 and day 28 were not significant, indicating non-systemic toxicity. In conclusion, HC-HT CSNP AQ cream is safe, well-tolerated, and non-toxic, which may be useful in treating atopic dermatitis.
Fulltext Potential of Nanoparticles Integrated with Antibacterial Properties in Preventing Biofilm and Antibiotic Resistance

Thambirajoo M, Maarof M, Lokanathan Y, Katas H, Ghazalli NF, Tabata Y, et al.

Antibiotics (Basel), 2021 Nov 02;10(11).
PMID: 34827276 DOI: 10.3390/antibiotics10111338

Nanotechnology has become an emerging technology in the medical field and is widely applicable for various clinical applications. The potential use of nanoparticles as antimicrobial agents is greatly explored and taken into consideration as alternative methods to overcome the challenges faced by healthcare workers and patients in preventing infections caused by pathogenic microorganisms. Among microorganisms, bacterial infections remain a major hurdle and are responsible for high morbidity and mortality globally, especially involving those with medical conditions and elderly populations. Over time, these groups are more vulnerable to developing resistance to antibiotics, as bacterial biofilms are difficult to destroy or eliminate via antibiotics; thus, treatment becomes unsuccessful or ineffective. Mostly, bacterial biofilms and other microbes can be found on medical devices and wounds where they disperse their contents which cause infections. To inhibit biofilm formations and overcome antibiotic resistance, antimicrobial-loaded nanoparticles alone or combined with other substances could enhance the bactericidal activity of nanomaterials. This includes killing the pathogens effectively without harming other cells or causing any adverse effects to living cells. This review summarises the mechanisms of actions employed by the different types of nanoparticles which counteract infectious agents in reducing biofilm formation and improve antibiotic therapy for clinical usage.
Oral Dispersible Films from Product Development to End-User Acceptability: A Review

Khan QU, Siddique MI, Sarfraz M, Rehman K, Sohail MF, Katas H

Crit Rev Ther Drug Carrier Syst, 2022;39(1):33-64.
PMID: 34936317 DOI: 10.1615/CritRevTherDrugCarrierSyst.2021036885

Orodispersible films (ODFs) have served as an emerging platform for the delivery of drugs in a convenient way. They have numerous advantages, the significant one is simplicity of administration for special populations such as pediatric and geriatric as well as patients with swallowing difficulty. Besides, the advantages include accurate dosing and fast action. The ODFs are efficiently designed with detailed knowledge of drug and polymers as well as a suitable selection of method. Many conventional and advance formulation strategies have been used for the development of ODFs. The biopharmaceutical concerns of active pharmaceutical ingredients (APIs) are given in this review in light of the fact that ODFs can be utilized to increase the bioavailability of APIs. The basic critical issues such as good mechanical properties, water solubility of the API and taste masking are very important to be considered during the development of ODFs. The knowledge of critical quality concerns of ODFs will be helpful in the future development of ODF. As ODFs remain in the mouth until complete degradation, taste, texture and mouth-feel are the qualities that in all respects liable for acceptability of the patient. An assortment of packaging choices is also accessible for ODFs. This review focuses on the different critical concerns of ODF related to composition, bio-pharmaceutical, manufacturing, quality tests, packaging and acceptability. Additionally, potential barriers in the ODFs development are discussed in details. Therefore, this review is an informative bundle of ODFs concerns from the product development stage to the end-user acceptability.
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.
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.
Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles

Siddique MI, Katas H, Amin MCIM, Ng SF, Zulfakar MH, Buang F, et al.

J Pharm Sci, 2015 Dec;104(12):4276-4286.
PMID: 26447747 DOI: 10.1002/jps.24666

Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.

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