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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.
Fulltext Dual-action of thermoresponsive gels containing DsiRNA-loaded gold nanoparticles for diabetic wound therapy: Characterization, in vitro safety and healing efficacy

Nor Azlan AYH, Katas H, Habideen NH, Mh Busra MF

Saudi Pharm J, 2020 Nov;28(11):1420-1430.
PMID: 33250649 DOI: 10.1016/j.jsps.2020.09.007

Diabetic wounds are difficult to treat due to multiple causes, including reduced blood flow and bacterial infections. Reduced blood flow is associated with overexpression of prostaglandin transporter (PGT) gene, induced by hyperglycaemia which causing poor vascularization and healing of the wound. Recently, gold nanoparticles (AuNPs) have been biosynthesized using cold and hot sclerotium of Lignosus rhinocerotis extracts (CLRE and HLRE, respectively) and capped with chitosan (CS) to produce biocompatible antibacterial nanocomposites. The AuNPs have shown to produce biostatic effects against selected gram positive and negative bacteria. Therefore, in this study, a dual therapy for diabetic wound consisting Dicer subtract small interfering RNA (DsiRNA) and AuNPs was developed to improve vascularization by inhibiting PGT gene expression and preventing bacterial infection, respectively. The nanocomposites were incorporated into thermoresponsive gel, made of pluronic and polyethylene glycol. The particle size of AuNPs synthesized using CLRE (AuNPs-CLRE) and HLRE (AuNPs-HLRE) was 202 ± 49 and 190 ± 31 nm, respectively with positive surface charge (+30 to + 45 mV). The thermoresponsive gels containing DsiRNA-AuNPs gelled at 32 ± 1 °C and released the active agents in sufficient amount with good texture and rheological profiles for topical application. DsiRNA-AuNPs and those incorporated into thermoresponsive pluronic gels demonstrated high cell viability, proliferation and cell migration rate via in vitro cultured cells of human dermal fibroblasts, indicating their non-cytotoxicity and wound healing properties. Taken together, the thermoresponsive gels are expected to be useful as a potential dressing that promotes healing of diabetic wounds.
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.
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.
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.
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.
In-vivo dermal pharmacokinetics, efficacy, and safety of skin targeting nanoparticles for corticosteroid treatment of atopic dermatitis

Siddique MI, Katas H, Amin MC, Ng SF, Zulfakar MH, Jamil A

Int J Pharm, 2016 Jun 30;507(1-2):72-82.
PMID: 27154252 DOI: 10.1016/j.ijpharm.2016.05.005

The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
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.
Dual Action Gels Containing DsiRNA Loaded Gold Nanoparticles: Augmenting Diabetic Wound Healing by Promoting Angiogenesis and Inhibiting Infection

Yasser Hamdi Nor Azlan A, Katas H, Mohamad Zin N, Fauzi Mh Busra M

Eur J Pharm Biopharm, 2021 Sep 25.
PMID: 34582971 DOI: 10.1016/j.ejpb.2021.09.007

Hyperglycemia induces the prostaglandin transporter (PGT) gene overexpression, leading to poor vascularization and wound healing. Dicer substrate small interfering RNA (DsiRNA) and gold nanoparticles (AuNPs) co-loaded into PF127 gel was developed to overcome the disturbance and infections. The AuNPs were biosynthesized using cold and hot water extracts of Lignosus rhinocerotis (abbreviated CLRE and HLRE, respectively). The wound healing efficacy of a PF127 gel containing DsiRNA-AuNPs-CLRE and -HLRE (assigned as F2 and F3, respectively) was evaluated in a diabetes-induced Wistar rat model. The F2 (DC) and F3 (DH) treated groups revealed a faster wound closure (92.67 ± 3.4% and 85.1 ± 7.3%, respectively) than the positive control (commercial gel, DTI)(74.9 ± 13.3%). DH and DC groups presented an increased blood vessel density, along with decreased inflammatory cells. In comparison to positive control, higher prostaglandin E2 (PGE2) (495 ±79 and 50 ±121 pg/mL, for DC and DH group, respectively), vascular endothelial growth factor (VEGF) (49 ±15 and 38 ±3 pg/mL, for DC and DH group, respectively) and VEGF-A levels were detected in both groups (DC and DH), indicating the effectiveness of DsiRNA in enhancing PGE2 production and vascularization. On evaluating microbiomes adhered to the wound areas, Gram-positive bacteria Staphylococcus and Corynebacterium, as well as Gram-negative Pseudomonas, Rodentibacter, and Acinetobacter, were found to be sensitive to the gel. Collectively, the gel was confirmed as a promising dressing for diabetic wound therapy, warranting further studies for clinical use.
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
Fulltext Antibacterial activity of biosynthesized gold nanoparticles using biomolecules from Lignosus rhinocerotis and chitosan

Katas H, Lim CS, Nor Azlan AYH, Buang F, Mh Busra MF

Saudi Pharm J, 2019 Feb;27(2):283-292.
PMID: 30766441 DOI: 10.1016/j.jsps.2018.11.010

A simple, cost-effective, and environmentally friendly method is needed for synthesizing metal nanoparticles, including gold nanoparticles (AuNPs). In this study, AuNPs were synthesized with Lignosus rhinocerotis sclerotial extract (LRE) and chitosan (CS) as reducing and stabilizing agents, respectively. Different LRE concentrations from cold and hot water extraction (CWE and HWE, respectively) were used to reduce chloroauric acid (HAuCl4) to form AuNPs. Positively charged chitosan stabilized AuNPs (CS-AuNPs) mediated by LRE exhibited a surface plasmon resonance (SPR) band at 533 nm. The CS-AuNPs synthesized using CWE had a smaller particle size (49.5 ± 6.7-82.4 ± 28.0 nm) compared to that of the HWE samples (80.3 ± 23.4-125.3 ± 41.5 nm), depending on LRE concentration. FTIR results suggested protein and polysaccharides in LRE were the sources of reducing power, reducing gold ions to AuNPs. CS-AuNPs were mostly spherical with higher LRE concentrations, whereas some triangular, pentagonal, irregular, and rod shaped AuNPs were observed at lower LRE concentrations. CS-AuNPs mediated by LRE displayed effective antibacterial activity against gram-negative (Pseudomonas aeruginosa and Escherichia coli) and gram-positive bacteria (Staphylococcus aureus and Bacillus sp.). Thus, the biosynthesized AuNPs using LRE and chitosan provide opportunities for developing stable and eco-friendly nanoparticles with effective antibacterial properties.
Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Shahid N, Siddique MI, Razzaq Z, Katas H, Waqas MK, Rahman KU

Drug Dev Ind Pharm, 2018 Dec;44(12):2061-2070.
PMID: 30081679 DOI: 10.1080/03639045.2018.1509081

OBJECTIVE: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.
SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.
METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.
RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.
CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.
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.
Gelatin Hydrogels Loaded with Lactoferrin-Functionalized Bio-Nanosilver as a Potential Antibacterial and Anti-Biofilm Dressing for Infected Wounds: Synthesis, Characterization, and Deciphering of Cytotoxicity

Suleman Ismail Abdalla S, Katas H, Chan JY, Ganasan P, Azmi F, Fauzi MB

Mol Pharm, 2021 05 03;18(5):1956-1969.
PMID: 33822631 DOI: 10.1021/acs.molpharmaceut.0c01033

Gelatin hydrogels are attractive for wound applications owing to their well-defined structural, physical, and chemical properties as well as good cell adhesion and biocompatibility. This study aimed to develop gelatin hydrogels incorporated with bio-nanosilver functionalized with lactoferrin (Ag-LTF) as a dual-antimicrobial action dressing, to be used in treating infected wounds. The hydrogels were cross-linked using genipin prior to loading with Ag-LTF and characterized for their physical and swelling properties, rheology, polymer and actives interactions, and in vitro release of the actives. The hydrogel's anti-biofilm and antibacterial performances against S. aureus and P. aeruginosa as well as their cytotoxicity effects were assessed in vitro, including primary wound healing gene expression of human dermal fibroblasts (HDFs). The formulated hydrogels showed adequate release of AgNPs and LTF, with promising antimicrobial effects against both bacterial strains. The Ag-LTF-loaded hydrogel did not significantly interfere with the normal cellular functions as no alteration was detected for cell viability, migration rate, and expression of the target genes, suggesting the nontoxicity of Ag-LTF as well as the hydrogels. In conclusion, Ag-LTF-loaded genipin-cross-linked gelatin hydrogel was successfully synthesized as a new approach for fighting biofilms in infected wounds, which may be applied to accelerate healing of chronic wounds.
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.
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 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.
Fulltext Characterisation of Rapid In Situ Forming Gelipin Hydrogel for Future Use in Irregular Deep Cutaneous Wound Healing

Nike DU, Katas H, Mohd NF, Hiraoka Y, Tabata Y, Idrus RBH, et al.

Polymers (Basel), 2021 Sep 17;13(18).
PMID: 34578052 DOI: 10.3390/polym13183152

The irregular deep chronic wound is a grand challenge to be healed due to multiple factors including slow angiogenesis that causing regenerated tissue failure. The narrow gap of deep wounds could hinder and slow down normal wound healing. Thus, the current study aimed to develop a polymerised genipin-crosslinked gelatin (gelipin) hydrogel (GNP_GH) as a potential biodegradable filler for the abovementioned limitations. Briefly, GNP_GH bioscaffolds have been developed successfully within three-minute polymerisation at room temperature (22-24 °C). The physicochemical and biocompatibility of GNP_GH bioscaffolds were respectively evaluated. Amongst GNP_GH groups, the 0.1%GNP_GH10% displayed the highest injectability (97.3 ± 0.6%). Meanwhile, the 0.5%GNP_GH15% degraded within more than two weeks with optimum swelling capacity (108.83 ± 15.7%) and higher mechanical strength (22.6 ± 3.9 kPa) than non-crosslinked gelatin hydrogel 15% (NC_GH15%). Furthermore, 0.1%GNP_GH15% offered higher porosity (>80%) and lower wettability (48.7 ± 0.3) than NC_GH15%. Surface and cross-section SEM photographs displayed an interconnected porous structure for all GNP_GH groups. The EDX spectra and maps represented no major changes after GNP modification. Moreover, no toxicity effect of GNP_GH against dermal fibroblasts was shown during the biocompatibility test. In conclusion, the abovementioned findings indicated that gelipin has excellent physicochemical properties and acceptable biocompatibility as an acellular rapid treatment for future use in irregular deep cutaneous wounds.
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.
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.

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