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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.
Biopolymer based nanoparticles and their therapeutic potential in wound healing - A review

Kumar M, Mahmood S, Chopra S, Bhatia A

Int J Biol Macromol, 2024 Apr 10;267(Pt 2):131335.
PMID: 38604431 DOI: 10.1016/j.ijbiomac.2024.131335

Nanoparticles (NPs) have been extensively investigated for their potential in nanomedicine. There is a significant level of enthusiasm about the potential of NPs to bring out a transformative impact on modern healthcare. NPs can serve as effective wound dressings or delivery vehicles due to their antibacterial and pro-wound-healing properties. Biopolymer-based NPs can be manufactured using various food-grade biopolymers, such as proteins, polysaccharides, and synthetic polymers, each offering distinct properties suitable for different applications which include collagen, polycaprolactone, chitosan, alginate, and polylactic acid, etc. Their biodegradable and biocompatible nature renders them ideal nanomaterials for applications in wound healing. Additionally, the nanofibers containing biopolymer-based NPs have shown excellent anti-bacterial and wound healing activity like silver NPs. These NPs represent a paradigm shift in wound healing therapies, offering targeted and personalized solutions for enhanced tissue regeneration and accelerated wound closure. The current review focuses on biopolymer NPs with their applications in wound healing.
Engineered liposomes mediated approach for targeted colorectal cancer drug Delivery: A review

Shazleen Ibrahim I, Starlin Chellathurai M, Mahmood S, Hakim Azmi A, Harun N, Ulul Ilmie Ahmad Nazri M, et al.

Int J Pharm, 2024 Feb 15;651:123735.
PMID: 38142874 DOI: 10.1016/j.ijpharm.2023.123735

Colorectal cancer (CRC) continues to be one of the most prevalent and deadliest forms of cancer worldwide, despite notable advancements in its management. The prognosis for metastatic CRC remains discouraging, with a relative 5-year survival rate for stage IV CRC patients. Conventional treatments for advanced malignancies such as chemotherapy, often face limitations in effectively targeting cancer cells resulting in off-target distribution and significant side effects. In the quest for better strategies, researchers have explored numerous alternatives. Among these, nanoparticles (NPs) specifically liposomes have emerged as one of the most promising candidates in developing targeted delivery systems for cancer therapeutics. This review discusses the current approaches employing functionalised liposomes to overcome major biological barriers in therapeutics delivery for CRC treatment. We have also shared our perspectives on the technological development of liposomes for future clinical use and highlighted a few useful insights on the material choices for future research work in CRC.
Marine-derived polysaccharides and their therapeutic potential in wound healing application - A review

Kumar M, Kumar D, Garg Y, Mahmood S, Chopra S, Bhatia A

Int J Biol Macromol, 2023 Dec 31;253(Pt 6):127331.
PMID: 37820901 DOI: 10.1016/j.ijbiomac.2023.127331

Polysaccharides originating from marine sources have been studied as potential material for use in wound dressings because of their desirable characteristics of biocompatibility, biodegradability, and low toxicity. Marine-derived polysaccharides used as wound dressing, provide several benefits such as promoting wound healing by providing a moist environment that facilitates cell migration and proliferation. They can also act as a barrier against external contaminants and provide a protective layer to prevent further damage to the wound. Research studies have shown that marine-derived polysaccharides can be used to develop different types of wound dressings such as hydrogels, films, and fibres. These dressings can be personalised to meet specific requirements based on the type and severity of the wound. For instance, hydrogels can be used for deep wounds to provide a moist environment, while films can be used for superficial wounds to provide a protective barrier. Additionally, these polysaccharides can be modified to improve their properties, such as enhancing their mechanical strength or increasing their ability to release bioactive molecules that can promote wound healing. Overall, marine-derived polysaccharides show great promise for developing effective and safe wound dressings for various wound types.
Strategies to improve the stability of amorphous solid dispersions in view of the hot melt extrusion (HME) method

Al-Japairai K, Hamed Almurisi S, Mahmood S, Madheswaran T, Chatterjee B, Sri P, et al.

Int J Pharm, 2023 Nov 25;647:123536.
PMID: 37865133 DOI: 10.1016/j.ijpharm.2023.123536

Oral administration of drugs is preferred over other routes for several reasons: it is non-invasive, easy to administer, and easy to store. However, drug formulation for oral administration is often hindered by the drug's poor solubility, which limits its bioavailability and reduces its commercial value. As a solution, amorphous solid dispersion (ASD) was introduced as a drug formulation method that improves drug solubility by changing the molecular structure of the drugs from crystalline to amorphous. The hot melt extrusion (HME) method is emerging in the pharmaceutical industry as an alternative to manufacture ASD. However, despite solving solubility issues, ASD also exposes the drug to a high risk of crystallisation, either during processing or storage. Formulating a successful oral administration drug using ASD requires optimisation of the formulation, polymers, and HME manufacturing processes applied. This review presents some important considerations in ASD formulation, including strategies to improve the stability of the final product using HME to allow more new drugs to be formulated using this method.
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.
Correction: Therapeutic Potential of Nanocarrier-Mediated Delivery of Phytoconstituents for Wound Healing: Their Current Status and Future Perspective

Kumar M, Keshwania P, Chopra S, Mahmood S, Bhatia A

AAPS PharmSciTech, 2023 Oct 05;24(7):206.
PMID: 37798593 DOI: 10.1208/s12249-023-02668-8
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.
Environmental implication and cancer risk assessment of residual pollutants in cotton crop: a case study of Multan District, Pakistan

Parveen A, Anjum M, Mahmood S, Nawaz R, Khalid A

Environ Monit Assess, 2023 Aug 26;195(9):1100.
PMID: 37632590 DOI: 10.1007/s10661-023-11710-y

Pakistan is the fourth largest yarn producer in the world heavily that relies on cotton crop which receives a substantial 62% of all pesticide applications. The present study was conducted to quantify the levels of pesticides such as bifenthrin, spirotetramat, pyriproxyfen, imidacloprid, and diafenthiuron in soil and plants residue at selected cotton fields of Multan District, Pakistan. In addition to pesticides, the assessment of heavy metal concentration was also conducted in order to determine the overall risks that these compounds to both plants and human population. For this analysis, 20 soil samples and 10 plant samples were collected from 10 selected cotton fields. Pesticides and heavy metals in soil and plant samples were analyzed using high-performance liquid chromatography (HPLC) and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), respectively. It was observed that all samples collected from selected fields contained pesticide residue in top soil (0-15 cm). However, no pesticides were detected in the lower soil layer (16-30 cm). In case of heavy metals, the highest concentration of Fe, Pb, and Mn was observed in both soil and plant residue samples. The heavy metals were found in the order of Fe > Mn > Pb > Zn > Cu > Cd in the soil. The total carcinogenic risk values for a few pesticides were found to range from 10-6 to 10-2, indicating that residents of the study area have low to higher chances of developing cancer. A positive correlation was observed among the pesticides (r = 0.18-0.95) as well as in metals related parameters (r = 0.49-0.96), where a weak negative correlation was found among metal to pesticide parameters except Pd where the maximum r value was 0.62. In general, the finding of this study encourages the development and adoption of sustainable agricultural practices that lower the dependence on toxic pesticides and endorse environmentally friendly alternatives.
Therapeutic Potential of Nanocarrier-Mediated Delivery of Phytoconstituents for Wound Healing: Their Current Status and Future Perspective

Kumar M, Keshwania P, Chopra S, Mahmood S, Bhatia A

AAPS PharmSciTech, 2023 Jul 20;24(6):155.
PMID: 37468691 DOI: 10.1208/s12249-023-02616-6

The treatment of wounds is a serious problem all over the world and imposes a huge financial burden on each and every nation. For a long time, researchers have explored wound dressing that speeds up wound healing. Traditional wound dressing does not respond effectively to the wound-healing process as expected. Therapeutic active derived from plant extracts and extracted bioactive components have been employed in various regions of the globe since ancient times for the purpose of illness, prevention, and therapy. About 200 years ago, most medical treatments were based on herbal remedies. Especially in the West, the usage of herbal treatments began to wane in the 1960s as a result of the rise of allopathic medicine. In recent years, however, there has been a resurgence of interest in and demand for herbal medicines for a number of reasons, including claims about their efficacy, shifting consumer preferences toward natural medicines, high costs and negative side effects of modern medicines, and advancements in herbal medicines brought about by scientific research and technological innovation. The exploration of medicinal plants and their typical uses could potentially result in advanced pharmaceuticals that exhibit reduced adverse effects. This review aims to present an overview of the utilization of nanocarriers in plant-based therapeutics, including its current status, recent advancements, challenges, and future prospects. The objective is to equip researchers with a comprehensive understanding of the historical background, current state, and potential future developments in this emerging field. In light of this, the advantages of nanocarriers based delivery of natural wound healing treatments have been discussed, with a focus on nanofibers, nanoparticles, nano-emulsion, and nanogels.
Self-assembled chitosan-insulin oral nanoparticles - A critical perspective review

Chellathurai MS, Yong CL, Sofian ZM, Sahudin S, Hasim NBM, Mahmood S

Int J Biol Macromol, 2023 Jul 15;243:125125.
PMID: 37263321 DOI: 10.1016/j.ijbiomac.2023.125125

Chitosan is an abundant natural cationic polysaccharide with excellent biodegradability, bioadhesion, and biocompatibility. Chitosan is extensively researched for various particulate oral insulin drug delivery systems. Oral insulin is economically efficient and more convenient than injections, with greater patient compliance. Electrostatic ionic interaction between cationic chitosan and anionic polymer or insulin leads to the formation of spontaneously self-assembled nanoparticles. This simple technique attracted many researchers as it can be carried out quickly in mild conditions without harmful solvents, such as surfactants or chemical cross-linkers that might degrade the insulin structure. The formulated chitosan nanoparticles help to protect the core insulin from enzymatic degradation in the digestive system and improve paracellular intestinal uptake from the enterocytes due to mucoadhesion and reversible tight junction opening. Moreover, functionalized chitosan nanoparticles create newer avenues for targeted and prolonged delivery. This review focuses on modified chitosan-insulin nanoparticles and their implications on oral insulin delivery. Dependent variables and their optimal concentration ranges used in self-assembly techniques for chitosan-insulin nanoparticular synthesis are summarized. This review provides a comprehensive guide to fine-tune the essential factors to formulate stable insulin-chitosan nanoparticles using mild ionic interactions.
Gold nanoparticles-based photothermal therapy for breast cancer

Dheyab MA, Aziz AA, Khaniabadi PM, Jameel MS, Oladzadabbasabadi N, Rahman AA, et al.

Photodiagnosis Photodyn Ther, 2023 Jun;42:103312.
PMID: 36731732 DOI: 10.1016/j.pdpdt.2023.103312

AuNPs-mediated photothermal therapy (PTT) is gaining popularity in both laboratory research and medical applications. It has proven clear advantages in breast cancer therapy over conventional thermal ablation because of its easily-tuned features of irradiation light with inside hyperthermia ability. Notwithstanding this significant progress, the therapeutic potential of AuNPs-mediated PTT in cancer treatments is still impeded by several challenges, including inherent non-specificity, low photothermal conversion effectiveness, and the limitation of excitation light tissue penetration. Given the rapid progress of AuNPs-mediated PTT, we present a comprehensive overview of significant breakthroughs in the recent advancements of AuNPs for PTT, focusing on breast cancer cells. With the improvement of chemical synthesis technology, AuNPs of various sizes and shapes with desired properties can be synthesized, allowing breast cancer targeting and treatment. In this study, we summarized the different sizes and features of four major types of AuNPs in this review: Au nanospheres, Au nanocages, Au nanoshells, and Au nanorods, and explored their benefits and drawbacks in PTT. We also discussed the diagnostic, bioconjugation, targeting, and cellular uptake of AuNPs, which could improve the performance of AuNP-based PTT. Besides that, potential challenges and future developments of AuNP-mediated PTT for clinical applications are discussed. AuNP-mediated PTT is expected to become a highly promising avenue in cancer treatment in the near future.
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.
Monte Carlo simulation of gold nanoparticles for X-ray enhancement application

Dheyab MA, Aziz AA, Rahman AA, Ashour NI, Musa AS, Braim FS, et al.

Biochim Biophys Acta Gen Subj, 2023 Apr;1867(4):130318.
PMID: 36740000 DOI: 10.1016/j.bbagen.2023.130318

BACKGROUND: Gold nanoparticles (Au NPs) are regarded as potential agents that enhance the radiosensitivity of tumor cells for theranostic applications. To elucidate the biological mechanisms of radiation dose enhancement effects of Au NPs as well as DNA damage attributable to the inclusion of Au NPs, Monte Carlo (MC) simulations have been deployed in a number of studies.
SCOPE OF REVIEW: This review paper concisely collates and reviews the information reported in the simulation research in terms of MC simulation of radiosensitization and dose enhancement effects caused by the inclusion of Au NPs in tumor cells, simulation mechanisms, benefits and limitations.
MAJOR CONCLUSIONS: In this review, we first explore the recent advances in MC simulation on Au NPs radiosensitization. The MC methods, physical dose enhancement and enhanced chemical and biological effects is discussed, followed by some results regarding the prediction of dose enhancement. We then review Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation. Moreover, we explain and look at Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation.
GENERAL SIGNIFICANCE: Using advanced chemical module-implemented MC simulations, there is a need to assess the radiation-induced chemical radicals that contribute to the dose-enhancing and biological effects of multiple Au NPs.
Psychometric validation of revised Olweus Bully/Victim Questionnaire (OBVQ-R) among adolescents in Bangladesh

Mahmood S, Siraji MA, Naher R, Arató N, Kaló Z

Asian J Psychiatr, 2023 Feb 17;83:103514.
PMID: 36906995 DOI: 10.1016/j.ajp.2023.103514

BACKGROUND: The assessment of bullying-related attributes is vital in developing anti-bullying intervention and prevention programs. The revised Olweus Bully/Victim Questionnaire (OBVQ-R) is one tool that has been widely used for this purpose. Thus, as we noticed a rising interest in research on bullying and there is a scarcity of proper psychometric tools to assess bullying-related attributes in Bangladesh, our study aimed to translate the OBVQ-R and test the psychometric properties of the Bangla version of this questionnaire on a large Bangladeshi adolescent sample.
METHOD: In Bangladesh, we collected data from grade 8-10 students (N = 567, 309 females, 258 males, AgeMean±SD=15.12 ± 0.81). The participants completed Bangla OBVQ-R, Beck Youth Inventory (BYI), and Children's Revised Impact of Events Scale-13 (CRIES-13).
RESULTS: The item response theory (IRT) analysis discarded five items and retained 15 items (Victimization=8, Perpetration=7). Both subscales had items with high discrimination (Victimization: 3.14 ± 0.67; Perpetration: 3.40 ± 1.04). Confirmatory factor analysis supported a correlated two-factor model (CFI=0.99; TLI=0.99). Both subscales (Victimization and Perpetration) and the 15-item full scale exhibited satisfactory reliability (>0.80). In line with our predictions, both subscales demonstrated significant positive correlations with BYI and CRIES-13, indicating satisfactory concurrent validity.
CONCLUSION: The results of the psychometric analyses supported the reliability and validity of the 15-item Bangla-version OBVQ-R to assess bullying involvement. Hence, this new, adapted measurement can facilitate further bullying research in Bangladesh and, thus, the development of prevention and intervention programs.
A review on taste masked multiparticulate dosage forms for paediatric

Al-Japairai K, Hamed Almurisi S, Almonem Doolaanea A, Mahmood S, Alheibshy F, Alobaida A, et al.

Int J Pharm, 2023 Feb 05;632:122571.
PMID: 36587776 DOI: 10.1016/j.ijpharm.2022.122571

Taste refers to those sensations perceived through taste buds on the tongue and oral cavity. The unpleasant taste of drugs leads to the refusal of taking the medicine in the paediatric population. It is widely known that a pharmaceutical product's general acceptability is the result of numerous contributing components such as swallowability, palatability (taste, flavour, texture, and mouthfeel), appearance, ease of administration, and patient characteristics. Multiparticulate as a dosage form is a platform technology for overcoming paediatrics' incapacity to swallow monolithic dosage forms, masking many medications' inherent nasty taste, and overcoming the obstacles of manufacturing a commercially taste masked dosage form. This review will discuss the considerations that must be taken into account to prepare taste masked multiparticulate dosage forms in the best way for paediatric use.
Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents

Akash S, Baeza J, Mahmood S, Mukerjee N, Subramaniyan V, Islam MR, et al.

Front Microbiol, 2023;14:1206872.
PMID: 37497547 DOI: 10.3389/fmicb.2023.1206872

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.
Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake

Khan AA, Akhtar S, Yadav Y, Atiya A, Alelwani W, Bannunah AM, et al.

Curr Drug Deliv, 2023;20(10):1474-1486.
PMID: 35980056 DOI: 10.2174/1567201819666220817111054

BACKGROUND: The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues.
METHODS: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.
RESULTS: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).
CONCLUSION: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.
Fulltext An application of fuzzy bipolar weighted correlation coefficient in decision-making problem

Mustafa S, Mahmood S, Salleh Z

PLoS One, 2023;18(12):e0283516.
PMID: 38113247 DOI: 10.1371/journal.pone.0283516

Diagnosing and finding the disease in medical sciences is a complex procedure. The basic steps involved in finding starts with signs, symptoms, and test. This study is based on the diagnosis of a skin disorder. The identification of a disease has been made on the basis of symptoms that sometimes show bipolarity. To address this bipolarity, the bipolar fuzzy sets are used as bipolar fuzzy sets cover the positive as well as negative aspects of a specific symptom. It is combined with the idea of soft sets, which gives more precise results. We have proposed a new technique in which a correlation coefficient is used to measure bipolar fuzzy soft set, which has been applied for diagnosis. The BFSSs deal most effectively with dual and fuzzy information. The correlation coefficient and the weighted correlation coefficient of BFSSs are suggested in this research. Based on said techniques, the decision-making method is suggested under a bipolar fuzzy environment to resolve ambiguous and unclear information. The implementation and effectiveness of the proposed and existing strategy has been checked by numerical computation.
Microbubbles: Revolutionizing Biomedical Applications with Tailored Therapeutic Precision

Kumar M, Kumar D, Chopra S, Mahmood S, Bhatia A

Curr Pharm Des, 2023;29(44):3532-3545.
PMID: 38151837 DOI: 10.2174/0113816128282478231219044000

BACKGROUND: Over the past ten years, tremendous progress has been made in microbubble-based research for a variety of biological applications. Microbubbles emerged as a compelling and dynamic tool in modern drug delivery systems. They are employed to deliver drugs or genes to targeted regions of interest, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials.
OBJECTIVE: The objective of this article is to review the microbubble compositions and physiochemical characteristics in relation to the development of innovative biomedical applications, with a focus on molecular imaging and targeted drug/gene delivery.
METHODS: The microbubbles are prepared by using various methods, which include cross-linking polymerization, emulsion solvent evaporation, atomization, and reconstitution. In cross-linking polymerization, a fine foam of the polymer is formed, which serves as a bubble coating agent and colloidal stabilizer, resulting from the vigorous stirring of a polymeric solution. In the case of emulsion solvent evaporation, there are two solutions utilized in the production of microbubbles. In atomization and reconstitution, porous spheres are created by atomising a surfactant solution into a hot gas. They are encapsulated in primary modifier gas. After the addition of the second gas or gas osmotic agent, the package is placed into a vial and sealed after reconstituting with sterile saline solution.
RESULTS: Microbubble-based drug delivery is an innovative approach in the field of drug delivery that utilizes microbubbles, which are tiny gas-filled bubbles, act as carriers for therapeutic agents. These microbubbles can be loaded with drugs, imaging agents, or genes and then guided to specific target sites.
CONCLUSION: The potential utility of microbubbles in biomedical applications is continually growing as novel formulations and methods. The versatility of microbubbles allows for customization, tailoring the delivery system to various medical applications, including cancer therapy, cardiovascular treatments, and gene therapy.

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