Deciphering the dynamics of methicillin-resistant Staphylococcus aureus biofilm formation: from molecular signaling to nanotherapeutic advances.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a global threat, necessitating the development of effective solutions to combat this emerging superbug. In response to selective pressures within healthcare, community, and livestock settings, MRSA has evolved increased biofilm formation as a multifaceted virulence and defensive mechanism, enabling the bacterium to thrive in harsh conditions. This review discusses the molecular mechanisms contributing to biofilm formation across its developmental stages, hence representing a step forward in developing promising strategies for impeding or eradicating biofilms. During staphylococcal biofilm development, cell wall-anchored proteins attach bacterial cells to biotic or abiotic surfaces; extracellular polymeric substances build scaffolds for biofilm formation; the cidABC operon controls cell lysis within the biofilm, and proteases facilitate dispersal. Beside the three main sequential stages of biofilm formation (attachment, maturation, and dispersal), this review unveils two unique developmental stages in the biofilm formation process for MRSA; multiplication and exodus. We also highlighted the quorum sensing as a cell-to-cell communication process, allowing distant bacterial cells to adapt to the conditions surrounding the bacterial biofilm. In S. aureus, the quorum sensing process is mediated by autoinducing peptides (AIPs) as signaling molecules, with the accessory gene regulator system playing a pivotal role in orchestrating the production of AIPs and various virulence factors. Several quorum inhibitors showed promising anti-virulence and antibiofilm effects that vary in type and function according to the targeted molecule. Disrupting the biofilm architecture and eradicating sessile bacterial cells are crucial steps to prevent colonization on other surfaces or organs. In this context, nanoparticles emerge as efficient carriers for delivering antimicrobial and antibiofilm agents throughout the biofilm architecture. Although metal-based nanoparticles have been previously used in combatting biofilms, its non-degradability and toxicity within the human body presents a real challenge. Therefore, organic nanoparticles in conjunction with quorum inhibitors have been proposed as a promising strategy against biofilms. As nanotherapeutics continue to gain recognition as an antibiofilm strategy, the development of more antibiofilm nanotherapeutics could offer a promising solution to combat biofilm-mediated resistance.

Nanocarriers for the treatment of glioblastoma multiforme: A succinct review of conventional and repositioned drugs in the last decade.

Glioblastoma multiforme is a very combative and threatening type of cancer. The standard course of treatment involves excising the tumor surgically, then administering chemotherapy and radiation therapy. Because of the presence of the blood-brain barrier and the unique characteristics of the tumor microenvironment, chemotherapy is extremely difficult and has a high incidence of relapse. With their capacity to precisely target and transport therapeutic medications to the tumor while overcoming the challenges provided by invasive and infiltrative gliomas, nanocarriers offer a potentially beneficial treatment option for gliomas. Drug repositioning or, in other words, finding novel therapeutic uses for medications that have received approval for previous uses has also recently emerged to provide alternative treatments for many diseases, with glioblastoma being among them. In this article, our goal is to shed light on the pathogenesis of glioma and summarize the proposed treatment approaches in the last decade, highlighting how combining repositioned drugs and nanocarriers technology can reduce drug resistance and improve therapeutic efficacy in primary glioma.

Developing a rapid analytical method for simultaneous determination of apigenin and gallic acid: validation and application in a nanoliposomal formulation.

OBJECTIVE: Apigenin and gallic acid are natural compounds that are useful as antioxidant, anti-inflammatory and anticancer agents, especially when used together in combination. Therefore, the development and validation of a simultaneous method of analysis for both compounds in pure form and when encapsulated in an advanced delivery system such as liposomes would be useful. METHODS: Analysis was performed using C18 column under isocratic conditions. The mobile phase was acetonitrile: water containing 0.2% orthophosphoric acid at a ratio of 67:33, flow rate 1 ml/min, and detection wavelength 334 nm for apigenin and 271 nm for gallic acid. RESULTS: The assay method was linear at the concentration range (5-600 µg/mL) with R2 of 1 for both drugs. The method was also shown to be precise and robust with RSD less than 2% with LOD (0.12, 0.1 µg/mL) and LOQ (4.14, 3.58 µg/mL) for apigenin and gallic acid respectively. The method was also applicable for the determination of the entrapment efficiency of both drugs when co-loaded in a nanoliposomal formulation. CONCLUSION: The described HPLC method was shown to be suitable, sensitive, and reproducible for the simultaneous identification and quantification of apigenin and gallic acid. The analytical results were accurate and precise, with good recovery, low limit of detection, and the chromatographic assay was accomplished in less than 3 min, suggesting the suitability of the method for routine analysis of both drugs in pharmaceutical formulations.

Ferulic acid nanoemulsion as a promising anti-ulcer tool: in vitro and in vivo assessment.

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.

Curcumin-resveratrol nano-formulation counteracting hyperammonemia in rats.

Malnutrition and low dietary protein intake could be risk factors for developing peripheral and central hyperammonemia, especially in pediatrics. Both curcumin and resveratrol proved to be effective against several hepatic and cerebral injuries. They were reported to be beneficial in lowering circulating ammonia levels, yet both are known for their low bioavailability. The use of pharmaceutical nano-formulations as delivery systems for these two nutraceuticals could solve the aforementioned problem. Hence, the present study aimed to investigate the valuable outcome of using a combination of curcumin and resveratrol in a nanoemulsion formulation, to counteract protein-deficient diet (PDD)-induced hyperammonemia and the consequent complications in male albino rats. Results revealed that using a nanoemulsion containing both curcumin and resveratrol at a dose of (5 + 5 mg/kg) effectively reduced hepatic and brain ammonia levels, serum ALT and AST levels, hepatic and brain nitric oxide levels, oxidative DNA damage as well as disrupted cellular energy performance. In addition, there was a substantial increase in brain levels of monoamines, and a decrease in glutamate content. Therefore, it can be concluded that the use of combined curcumin and resveratrol nanoemulsion is an effective means of ameliorating the hepatic and cerebral adverse effects resulting from PDD-induced hyperammonemia in rats.

Combating hematopoietic and hepatocellular abnormalities resulting from administration of cisplatin: role of liver targeted glycyrrhetinic acid nanoliposomes loaded with amino acids.

The effectiveness of cisplatin in cancer treatment renders its use vital to clinicians. However, the accompanying side effects as cachexia, emesis and liver damage necessitate the use of a dietary supplement which is capable of hindering such undesirable complications. The branched chain amino acids as well as glutamine and arginine have been proven to be effective nutritional co-adjuvant therapeutic agents. Furthermore, new pharmaceutical approaches encompass designing organ-targeted nanoformulations to increase the medicinal efficacy. Therefore, the aim of the present study was to investigate the beneficial effects of liver-targeted amino acids-loaded nanoliposomes in counteracting the adverse hematopoietic and hepatic complications associated with cisplatin. Results revealed the use of the combination of two nanoliposomal formulations (one loading leucine + isolecuine + valine, and the other loading glutamine and arginine) given orally at a dose of 200 mg/kg for twelve days was effective against cisplatin-induced toxicities represented by improvement in the complete blood picture parameters, decrease in the serum hepatic enzymes levels, amelioration of the hepatic oxidative stress and cellular energy imbalance along with reduction in the histopathological abnormalities. It can be concluded that amino acids loaded nanoliposomes could be considered a new strategy in preventing cisplatin's adverse effects.

Insightful exploring of advanced nanocarriers for the topical/transdermal treatment of skin diseases.

Dermatological products constitute a big segment of the pharmaceutical market. From conventional products to more advanced ones, a wide variety of dosage forms have been developed till current date. A representative of the advanced delivery means is carrier-based systems, which can load large number of drugs for treatment of dermatological diseases, or simply for cosmeceutical purposes. To make them more favorable for topical delivery, further incorporation of these carriers in a topical vehicle, such as gels or creams is made. Therefore in this review article, an overview is compiled of the most commonly encountered novel carrier based topical delivery systems; namely lipid based (nanoemulsions, microemulsions, solid lipid nanoparticles [SLNs] and nanostructured lipid carriers [NLCs]), and vesicular carriers (non-deformable, such as liposomes, niosomes, emulsomes and cerosomes, and deformable, such as transfersomes, ethosomes, transethosomes, and penetration enhancer vesicles), with special emphasis on those loaded in a secondary gel vehicle. A special focus was made on the commonly encountered dermatological diseases, such as bacterial and fungal infections, psoriasis, dermatitis, eczema, vitiligo, oxidative damage, aging, alopecia, and skin cancer.

Fabrication of extended-dissolution divalproex tablets: a green solvent-free granulation technique.

Objective: Divalproex sodium (DVS) is a challenging drug owing to its hygroscopicity, bitter taste, and short in vivo half-life. This study aims to produce stable taste masked DVS once daily tablets using solvent free hot melt granulation (HMG) process.Methods: A lab scale high shear mixer granulator employing six meltable lipid binders (compritol®888 ATO, beeswax, gelucire®50/13, precirol® ATO5, stearyl alcohol, and geleol®) was used for the preparation of tablets. Quality control tests were performed on granules and tablets, and Box-Behnken's design was adopted to investigate the effect of binder concentration, impeller speed, and granulation time on the drug dissolution. Shelf and accelerated stability evaluation, taste assessment, and in vivo pharmacokinetic study were conducted on the selected batches.Results: Results revealed that DVS tablets were successfully prepared, and that the in vitro dissolution of the drug was inversely proportional to the binder concentration. Beeswax and compritol® tablets showed similar dissolution profiles to the marketed product Depakote® 500 ER tablets (F1 < 15 and F2 > 50). The selected batches showed lower moisture content (<2%) and successfully masked the bitter taste compared to uncoated tablets based on a hydrophilic matrix. The in vivo pharmacokinetic study delineated relative bioavailability values for Beeswax and Compritol® tablets of 95.6% and 118%, respectively, compared to the marketed product.Conclusion: The solvent free HMG process can be employed to formulate 24 h extended dissolution DVS tablets with masked bitter taste and high stability, and comparable or higher bioavailability than the marketed product.

In vitro anti-inflammatory potential of phloretin microemulsion as a new formulation for prospective treatment of vaginitis.

Phloretin is a promising polyphenolic compound known for its anti-inflammatory properties, but its poor solubility and low bioavailability hinder its clinical applicability. Till current date, its potential in the treatment of vaginitis has not been explored, and only very few papers reported its formulation as nanoparticles to overcome its pharmaceutical challenges. Therefore, in the current study, phloretin was formulated in microemulsion of 11 nm size, and its in vitro anti-inflammatory properties were explored using histamine and IL-6 release inhibition assays, protease inhibition assay, and membrane stabilization potential. The anti-inflammatory properties of phloretin microemulsion were compared to the drug phloretin, and the reference standard non-steroidal anti-inflammatory drugs (NSAIDs). Results proved that both phloretin and phloretin microemulsion significantly inhibited the release of the inflammatory mediators histamine and IL-6, inhibited protease action, and exhibited membrane stabilization potential. Phloretin microemulsion exhibited comparable anti-inflammatory properties to the NSAIDs diclofenac and indomethacin, and, hence, it can be delineated as a promising therapeutic tool in topical treatment of vaginal inflammation.

Nicotinamide extrudates as novel anti-aging and collagen promoting platform: a comparative cosmeceutical study versus the gel form.

The objective of the study was to explore the potential of a novel nicotinamide extrudate as an anti-aging platform compared to the conventional gel. Nicotinamide extrudates were prepared by hot melt extrusion and characterized pharmaceutically for their thermal behavior, mositure uptake, skin adhesion, and deposition in different skin layers. The pharmacological potential of the extrudates was explored in terms of induction of skin amino acids, cellular energy estimation, 8-hydroxy-2-deoxyguanosine content, Nitrate + nitrite content and histological chacaterization of collagen area percent. Results revealed that the extrusion technique managed to amorphize nicotinamide and enhance its skin deposition (46%) compared to the gel form which only showed about 10% deposition, owing to the mucoadhesive nature of the former. Extrudates were also found superior to the gel form as demonstrated by the increased amino acids level (glycine, proline, hydroxyproline), increased cellular energy, decreased oxidative stress and increased collagen formation. Nictotinamide extrudates were proven to be a scalable promising anti-aging platform which are worthy of entering the cosmeceutical market as products.

Fabrication of rosuvastatin-loaded polymeric nanocapsules: a promising modality for treating hepatic cancer delineated by apoptotic and cell cycle arrest assessment.

Nanotechnology has provided several advantages for the treatment of cancer. Polymeric nanocapsules (PNCs) were proven promising in the treatment of different cancer types, such as hepatic cancer. Meanwhile, the exploration of novel indications of old molecules with the purpose of cancer treatment has been widely reported. Among the promising therapeutic moieties, rosuvastatin (RV) was delineated as a potential anticancer drug. Hence, the target of the presented manuscript was to develop PNCs loaded with RV to overcome its delivery challenges and augment its anticancer activity. RV PNCs were fabricated by the nanoprecipitation method using poly-lactide-co-glycolide (PLGA) polymer, and were characterized for the size, polydispersity index (PDI), charge, entrapment efficiency EE%, in vitro release, stability, and morphology. Furthermore, their anticancer activity was tested on HepG2 cells using MTT assay, followed by elucidating the cytotoxic activity using flow cytometry. Results showed that RV PNCs displayed particle size ranging from 186 to 239 nm, average PDI, and negative zeta potential with sufficient stability for 3 months. PNCs were able to load RV at high EE% reaching 82.6% and sustain its release for eight hours. RV PNCs were superior in their anticancer activity on HepG2 cells, as delineated from the viability study and further elucidated by enhanced apoptosis in addition to cell cycle arrest at G2/M phase, suggesting their promise in treatment of hepatic cancer.

Comparative enhancement of curcumin cytotoxic photodynamic activity by nanoliposomes and gold nanoparticles with pharmacological appraisal in HepG2 cancer cells and Erlich solid tumor model.

Curcumin is a natural pigment that generates singlet oxygen upon light excitation, hence it can be used as a photosensitizer in photodynamic therapy. The extremely low water solubility and poor systemic bioavailability make curcumin a challenging molecule to be used clinically. In this study, two nanocarrier systems for curcumin were prepared and characterized; nanoliposomes and polyvinyl pyrrolidone-capped gold nanoparticles. The dark and photocytotoxicity were investigated as a function of light fluence rate (100 and 200 mW/cm2) on HepG2 cancer cells. In vivo Erlich tumor model was developed and comparison of the tumor volume, survival rate, and histopathological alterations was made for the two nanocarriers. Results showed that both curcumin nanocarriers were successfully prepared and characterized. Light irradiation was able to augment the cytotoxicity of both curcumin liposomes and gold nanoparticles, with the former being superior in cytotoxicity compared to the latter. The tumor size was almost diminished 1 month post-photodynamic treatment for both systems with regression in the number of tumor cells upon histopathological evaluation, with curcumin liposomes producing better tumor regression than gold nanoparticles with comparable survival rate. Liposomes were confirmed to be superior to gold nanoparticles as a photodynamic treatment modality for cancer.

Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.

BACKGROUND: Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. METHODS: Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2ndgroup; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. RESULTS: PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was confirmed by histological examination and revealed pathological alteration in the PDD group. Ingestion of curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (P< 0.05) amelioration effects against PDD-induced disrupted reproductive performance as well as biochemical and pathological alterations and the overall results of the nano-emulsion (5 mg/kg) were comparable to curcumin (50 mg/kg). CONCLUSIONS: The present study suggests that administration of curcumin nano-emulsion as a daily supplement would be beneficial in malnutrition- induced troubled male reproductive performance and spermatogenesis cases.

Efficacy of Intravitreal injection of 2-Methoxyestradiol in regression of neovascularization of a retinopathy of prematurity rat model.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. METHODS: A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat. ROP was induced in 21 rats then two concentrations of 2-ME nanoparticles were injected in right eyes of 14 rats (low dose; study group I, high dose; study group II). A blank nanoemulsion was injected in the right eyes of seven rats (control positive group I). No injections performed in contralateral left eyes (control positive group II). Seven rats (14 eyes) were kept in room air (control negative group). On postnatal day 17, eyeballs were enucleated. Histological structure of the retina was examined using Hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP) expressions were detected by immunohistochemical studies. RESULTS: Intravitreal injection of 2-ME (in the two concentrations) caused marked regression of the new vascular tufts on the vitreal side with normal organization and thickness of the retina especially in study group II, which also show negative VEGF immunoreaction. Positive GFAP expression was detected in the control positive groups and study group (I). CONCLUSION: Intravitreal injection of 2-Methoxyestradiol nanoemulsion is a promising effective method in reduction of neovascularization of a ROP rat model.

Topical colloidal indocyanine green-mediated photodynamic therapy for treatment of basal cell carcinoma.

Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (∼125 nm) and a negative zeta potential (∼-31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC.

Optimizing the dermal accumulation of a tazarotene microemulsion using skin deposition modeling.

CONTEXT: It is well known that microemulsions are mainly utilized for their transdermal rather than their dermal drug delivery potential due to their low viscosity, and the presence of penetration enhancing surfactants and co-surfactants. OBJECTIVE: Applying quality by design (QbD) principles, a tazarotene microemulsion formulation for local skin delivery was optimized by creating a control space. MATERIALS AND METHODS: Critical formulation factors (CFF) were oil, surfactant/co-surfactant (SAA/CoS), and water percentages. Critical quality attributes (CQA) were globular size, microemulsion viscosity, tazarotene skin deposition, permeation, and local accumulation efficiency index. RESULTS AND DISCUSSION: Increasing oil percentage increased globular size, while the opposite occurred regarding SAA/CoS, (p = 0.001). Microemulsion viscosity was reduced by increasing oil and water percentages (p < 0.05), due to the inherent high viscosity of the utilized SAA/CoS. Drug deposition in the skin was reduced by increasing SAA/CoS due to the increased hydrophilicity and viscosity of the system, but increased by increasing water due to hydration effect (p = 0.009). Models with very good fit were generated, predicting the effect of CFF on globular size, microemulsion viscosity, and drug deposition. A combination of 40% oil and 45% SAA/CoS showed the maximum drug deposition of 75.1%. Clinical skin irritation study showed that the aforementioned formula was safe for topical use. CONCLUSION: This article suggests that applying QbD tools such as experimental design is an efficient tool for drug product design.

Deferasirox: A comprehensive drug profile.

Deferasirox is an iron-chelating drug developed by Novartis company for treatment of diseases accompanied by chronic iron overload; such as ß-thalassemia or sickle cell diseases. Owing to its advantages such as high affinity, specificity and wide therapeutic window, it is considered as first line treatment. The current chapter describes the physicochemical characteristics, mode of action, pharmacokinetics, therapeutic applications and synthetic methods for deferasirox. Moreover, it includes Fourier transform infrared spectrometry (FTIR) and nuclear magnetic resonance spectroscopy (NMR) analysis for its functional groups. In addition, the selected analytical methods are summarized to aid the analysts in their routine analysis of deferasirox.

Tailored green synthesized silymarin-selenium nanoparticles: Topical nanocarrier of promising antileishmanial activity.

Poor drug penetration, emerging drug resistance, and systemic toxicity are among the major obstacles challenging the current treatment of cutaneous leishmaniasis. Hence, developing advanced strategies for effective and targeted delivery of antileishmanial agents is crucial. Several drug delivery carriers have been developed till current date for dermal/transdermal delivery, especially those which are fabricated using eco-friendly synthesis approaches, since they protect the environment from the harmful effects of chemical waste disposal. This work describes the preparation of selenium nanoparticles loaded with silymarin via one-pot green reduction technique, for treatment of cutaneous leishmaniasis. The selected silymarin loaded selenium nanoparticles (SSNs4-0.1) displayed good loading efficiency of 58.22 ± 0.56 %, zeta potential of -30.63 ± 0.40 mV, hydrodynamic diameter of 245.77 ± 11.12 nm, and polydispersity index of 0.19 ± 0.01. It exhibited good physical stability, as well as high ex vivo deposition % in the epidermis (46.98 ± 1.51 %) and dermis (35.23 ± 1.72 %), which was further proven using confocal laser microscopy. It also exhibited significant cytocompatibility and noticeable cellular internalization of 90.02 ± 3.81 % in human fibroblasts, as well as high trypanothione reductase inhibitory effect (97.10 ± 0.30 %). Results of this study confirmed the successful green synthesis of silymarin-loaded selenium nanoparticles; delineating them as one of the promising antileishmanial topical delivery systems.

Recent progress on polySarcosine as an alternative to PEGylation: Synthesis and biomedical applications.

Biotherapeutic PEGylation to prolong action of medications has gained popularity over the last decades. Various hydrophilic natural polymers have been developed to tackle the drawbacks of PEGylation, such as its accelerated blood clearance and non-biodegradability. Polypeptoides, such as polysarcosine (pSar), have been explored as hydrophilic substitutes for PEG. pSar has PEG-like physicochemical characteristics such as water solubility and no reported cytotoxicity and immunogenicity. This review discusses pSar derivatives, synthesis, characterization approaches, biomedical applications, in addition to the challenges and future perspectives of pSar based biomaterials as an alternative to PEG.