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A review on polysaccharides mediated electrospun nanofibers for diabetic wound healing: Their current status with regulatory perspective

Kumar M, Hilles AR, Ge Y, Bhatia A, Mahmood S

Int J Biol Macromol, 2023 Apr 15;234:123696.
PMID: 36801273 DOI: 10.1016/j.ijbiomac.2023.123696

The current treatment strategies for diabetic wound care provide only moderate degree of effectiveness; hence new and improved therapeutic techniques are in great demand. Diabetic wound healing is a complex physiological process that involves synchronisation of various biological events such as haemostasis, inflammation, and remodelling. Nanomaterials like polymeric nanofibers (NFs) offer a promising approach for the treatment of diabetic wounds and have emerged as viable options for wound management. Electrospinning is a powerful and cost-effective method to fabricate versatile NFs with a wide array of raw materials for different biological applications. The electrospun NFs have unique advantages in the development of wound dressings due to their high specific surface area and porosity. The electrospun NFs possess a unique porous structure and biological function similar to the natural extracellular matrix (ECM), and are known to accelerate wound healing. Compared to traditional dressings, the electrospun NFs are more effective in healing wounds owing to their distinct characteristics, good surface functionalisation, better biocompatibility and biodegradability. This review provides a comprehensive overview of the electrospinning procedure and its operating principle, with special emphasis on the role of electrospun NFs in the treatment of diabetic wounds. This review discusses the present techniques applied in the fabrication of NF dressings, and highlights the future prospects of electrospun NFs in medicinal applications.
A review on chitosan and chitosan-based bionanocomposites: Promising material for combatting global issues and its applications

Azmana M, Mahmood S, Hilles AR, Rahman A, Arifin MAB, Ahmed S

Int J Biol Macromol, 2021 Aug 31;185:832-848.
PMID: 34237361 DOI: 10.1016/j.ijbiomac.2021.07.023

Over the last few years, several attempts have been made to replace petrochemical products with renewable and biodegradable components. The most challenging part of this approach is to obtain bio-based materials with properties and functions equivalent to those of synthetic products. Various naturally occurring polymers such as starch, collagen, alginate, cellulose, and chitin represent attractive candidates as they could reduce dependence on synthetic products and consequently positively impact the environment. Chitosan is also a unique bio-based polymer with excellent intrinsic properties. It is known for its anti-bacterial and film-forming properties, has high mechanical strength and good thermal stability. Nanotechnology has also applied chitosan-based materials in its most recent achievements. Therefore, numerous chitosan-based bionanocomposites with improved physical and chemical characteristics have been developed in an eco-friendly and cost-effective approach. This review discusses various sources of chitosan, its properties and methods of modification. Also, this work focuses on diverse preparation techniques of chitosan-based bionanocomposites and their emerging application in various sectors. Additionally, this review sheds light on future research scope with some drawbacks and challenges to motivate the researchers for future outstanding research works.
Synthesis of Capsaicin Loaded Silver Nanoparticles Using Green Approach and Its Anti-Bacterial Activity Against Human Pathogens

Mahmood S, Mei TS, Yee WX, Hilles AR, Alelwani W, Bannunah AM

J Biomed Nanotechnol, 2021 Aug 01;17(8):1612-1626.
PMID: 34544538 DOI: 10.1166/jbn.2021.3122

Nanotechnology is drawing attention nowadays due to its ability to regulate metals into nanosize, ultimately changing metal's physical, chemical, and optical properties. Silver nanoparticles are known for their potential impact as antimicrobial agents due to their inherent property penetrating the cell wall. The present study aimed to develop and statistically optimise using a novel combination of capsaicin loaded silver nanoparticles (AgCNPs) as an effective anti-bacterial agent to treat psoriasis using a green approach. Ascorbic acid was used as a reducing agent to fabricate silver nanoparticles. The formulation parameters optimisation was conducted using Box-Behnken Design (3×3 factorial design). The loading of capsaicin was confirmed by attenuated total reflectance-fourier transform infrared spectroscopy. Energy-dispersive X-ray spectroscopy-scanning electron microscopy (EDX-SEM) confirmed the existence of silver; net-like structure revealed in SEM and high-resolution transmission electron microscopy further confirmed the nano size of the formulation. Differential scanning calorimetry and X-ray diffraction demonstrated the capsaicin transformed into amorphous after encapsulated. An in-vitro microbial study showed that the 0.10 M formulation of AgCNPs exerted potent anti-bacterial activity, which can be considered an alternative anti-bacterial agent. It also displayed that the zone of inhibition was significantly high in gram-negative bacteria (E. coli) than gram-positive bacteria (S. aureus). Green synthesised AgCNPs showed highly significant anti-bacterial activity, which indicates that this formulation can be very promising for treating psoriasis.
Polymeric Nanoparticles for Brain Drug Delivery - A Review

Raman S, Mahmood S, Hilles AR, Javed MN, Azmana M, Al-Japairai KAS

Curr Drug Metab, 2020;21(9):649-660.
PMID: 32384025 DOI: 10.2174/1389200221666200508074348

BACKGROUND: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery.
METHODS: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs.
RESULTS: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain.
CONCLUSION: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.
Fulltext Ibuprofen-Loaded Chitosan-Lipid Nanoconjugate Hydrogel with Gum Arabic: Green Synthesis, Characterisation, In Vitro Kinetics Mechanistic Release Study and PGE2 Production Test

Mahmood S, Almurisi SH, Al-Japairai K, Hilles AR, Alelwani W, Bannunah AM, et al.

Gels, 2021 Dec 08;7(4).
PMID: 34940313 DOI: 10.3390/gels7040254

Ibuprofen is a well-known non-steroidal anti-inflammatory (NSAID) medicine that is often used to treat inflammation in general. When given orally, it produces gastrointestinal issues which lead to lower patient compliance. Ibuprofen transdermal administration improves both patient compliance and the efficacy of the drug. Nanoconjugation hydrogels were proposed as a controlled transdermal delivery tool for ibuprofen. Six formulations were prepared using different compositions including chitosan, lipids, gum arabic, and polyvinyl alcohol, through ionic interaction, maturation, and freeze-thaw methods. The formulations were characterised by size, drug conjugation efficiency, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Further analysis of optimised hydrogels was performed, including X-ray diffraction (XRD), rheology, gel fraction and swelling ability, in vitro drug release, and in vitro macrophage prostaglandin E2 (PGE2) production testing. The effects of ibuprofen's electrostatic interaction with a lipid or polymer on the physicochemical and dissolution characterisation of ibuprofen hydrogels were evaluated. The results showed that the S3 (with lipid conjugation) hydrogel provided higher conjugation efficiency and prolonged drug release compared with the S6 hydrogel.
Cationic starch: A functionalized polysaccharide based polymer for advancement of drug delivery and health care system - A review

Chatterjee S, Mahmood S, Hilles AR, Thomas S, Roy S, Provaznik V, et al.

Int J Biol Macromol, 2023 Sep 01;248:125757.
PMID: 37429342 DOI: 10.1016/j.ijbiomac.2023.125757

Research and development in health care industry is in persistence progression. To make it more patient-friendly or to get maximum benefits from it, special attention to different advanced drug delivery system (ADDS) is employed that delivers the drug at the target site and will be able to sustain/control release of drugs. ADDS should be non-toxic, biodegradable, biocompatible along with desirable showing physicochemical and functional properties. These drug delivery systems can be totally based on polymers, either with natural or synthetic polymers. The molecular weight of polymer can be tuned and different groups of polymers can be modified or substituted with other functional groups. Degree of substitution is also tailored. Cationic starch in recent years is exploited in drug delivery, tissue engineering and biomedicine. Due to their abundant availability, low cost, easy chemical modification, low toxicity, biodegradability and biocompatibility, extensive research is now being carried out. Our present discussion will shed light on the usage of cationic starch in health care system.
Fulltext PEGylated Lipid Polymeric Nanoparticle-Encapsulated Acyclovir for In Vitro Controlled Release and Ex Vivo Gut Sac Permeation

Mahmood S, Kiong KC, Tham CS, Chien TC, Hilles AR, Venugopal JR

AAPS PharmSciTech, 2020 Oct 14;21(7):285.
PMID: 33057878 DOI: 10.1208/s12249-020-01810-0

Currently, pharmaceutical research is directed wide range for developing new drugs for oral administration to target disease. Acyclovir formulation is having common issues of short half-life and poor permeability, causing messy treatment which results in patient incompliance. The present study formulates a lipid polymeric hybrid nanoparticles for antiviral acyclovir (ACV) agent with Phospholipon® 90G (lecithin), chitosan, and polyethylene glycol (PEG) to improve controlled release of the drugs. The study focused on the encapsulation of the ACV in lipid polymeric particle and their sustained delivery. The formulation developed for the self-assembly of chitosan and lecithin to form a shell encapsulating acyclovir, followed by PEGylation. Optimisation was performed via Box-Behnken Design (BBD), forming nanoparticles with size of 187.7 ± 3.75 nm, 83.81 ± 1.93% drug-entrapped efficiency (EE), and + 37.7 ± 1.16 mV zeta potential. Scanning electron microscopy and transmission electron microscopy images displayed spherical nanoparticles formation. Encapsulation of ACV and complexity with other physical parameters are confirmed through analysis using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. Nanoparticle produced was capable of achieving 24-h sustained release in vitro on gastric and intestinal environments. Ex vivo study proved the improvement of acyclovir's apparent permeability from 2 × 10-6 to 6.46 × 10-6 cm s-1. Acyclovir new formulation was achieved to be stable up to 60 days for controlled release of the drugs. Graphical abstract.
Fulltext Biomedical Application, Patent Repository, Clinical Trial and Regulatory Updates on Hydrogel: An Extensive Review

Mohapatra S, Mirza MA, Hilles AR, Zakir F, Gomes AC, Ansari MJ, et al.

Gels, 2021 Nov 12;7(4).
PMID: 34842705 DOI: 10.3390/gels7040207

Hydrogels are known for their leading role in biomaterial systems involving pharmaceuticals that fascinate material scientists to work on the wide variety of biomedical applications. The physical and mechanical properties of hydrogels, along with their biodegradability and biocompatibility characteristics, have made them an attractive and flexible tool with various applications such as imaging, diagnosis and treatment. The water-cherishing nature of hydrogels and their capacity to swell-contingent upon a few ecological signals or the simple presence of water-is alluring for drug conveyance applications. Currently, there are several problems relating to drug delivery, to which hydrogel may provide a possible solution. Hence, it is pertinent to collate updates on hydrogels pertaining to biomedical applications. The primary objective of this review article is to garner information regarding classification, properties, methods of preparations, and of the polymers used with particular emphasis on injectable hydrogels. This review also covers the regulatory and other commerce specific information. Further, it enlists several patents and clinical trials of hydrogels with related indications and offers a consolidated resource for all facets associated with the biomedical hydrogels.
Fulltext Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review

Mirza MA, Mahmood S, Hilles AR, Ali A, Khan MZ, Zaidi SAA, et al.

Pharmaceuticals (Basel), 2023 Nov 20;16(11).
PMID: 38004496 DOI: 10.3390/ph16111631

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.
Fulltext Biodegradable polymeric insulin microneedles - a design and materials perspective review

Starlin Chellathurai M, Mahmood S, Mohamed Sofian Z, Wan Hee C, Sundarapandian R, Ahamed HN, et al.

Drug Deliv, 2024 Dec;31(1):2296350.
PMID: 38147499 DOI: 10.1080/10717544.2023.2296350

Microneedle (MN) delivery devices are more accepted by people than regular traditional needle injections (e.g. vaccination) due to their simplicity and adaptability. Thus, patients of chronic diseases like diabetes look for alternative pain-free treatment regimens circumventing regular subcutaneous injections. Insulin microneedles (INS-MNs) are a thoughtfully researched topic (1) to overcome needle phobia in patients, (2) for controlled delivery of the peptide, (3) decreasing the frequency of drug administration, (4) to ease the drug administration procedure, and (5) thus increasing patient adherence to the treatment dosage regimes. MNs physically disrupt the hard outer skin layer to create minuscule pores for insulin (INS) to pass through the dermal capillaries into the systemic circulation. Biodegradable polymeric MNs are of greater significance for INS and vaccine delivery than silicon, metal, glass, or non-biodegradable polymeric MNs due to their ease of fabrication, mass production, cost-effectiveness, and bioerodability. In recent years, INS-MNs have been researched to deliver INS through the transdermal implants, buccal mucosa, stomach wall, intestinal mucosal layers, and colonic mucosa apart from the usual transdermal delivery. This review focuses on the design characteristics and the applications of biodegradable/dissolvable polymeric INS-MNs in transdermal, intra-oral, gastrointestinal (GI), and implantable delivery. The prospective approaches to formulate safe, controlled-release INS-MNs were highlighted. Biodegradable/dissolvable polymers, their significance, their impact on MN morphology, and INS release characteristics were outlined. The developments in biodegradable polymeric INS-MN technology were briefly discussed. Bio-erodible polymer selection, MN fabrication and evaluation factors, and other design aspects were elaborated.

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