Abstract:Purpose: The present study was designed to study the gentamycin (GTM)-loaded stimulusresponsive chitosan nanoparticles to treat bacterial conjunctivitis. Methods: GTM-loaded chitosan nanoparticles (GTM-CHNPs) were prepared by ionotropic gelation method and further optimized by 3-factor and 3-level Box-Behnken design. Chitosan (A), sodium tripolyphosphate (B), and stirring speed (C) were selected as independent variables. Their effects were observed on particle size (PS as Y1), entrapment efficiency (EE as Y2),… Show more
“…VCZ-loaded ultradeformable elastosomes were prepared according to a 3 3 Box-Behnken design using Design-Expert® software (Stat-Ease, Inc., Minneapolis, MN) to study the effect of different variables on vesicle properties. It was chosen as it aids in reducing the number of experimental runs needed for conducting the study, hence optimizing costs and saving time (Alruwaili et al., 2020 ; Radwan et al., 2020 ). Factors, their levels and desirability constraints are listed in Table 1 .…”
Voriconazole (VCZ) is a well-known broad spectrum triazole antifungal, mainly used orally and intravenously. The study aimed to formulate VCZ into ultradeformable elastosomes for the topical treatment of ocular fungal keratitis. Different formulae were prepared using a modified ethanol injection method, employing a 3
3
Box-Behnken design. They were characterized by measuring their entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The optimized formula was subjected to further
in vitro
investigations and
in vivo
evaluation studies. The prepared vesicles had satisfactory EE%, PS, PDI and ZP values. The numerical optimization process suggested an optimal elastosomal formula (OE) composed of phosphatidyl choline and brij S100 at the weight ratio of 3.62: 1, 0.25%w/v hyaluronic acid and 5% (percentage from phosphatidyl choline/brij mixture) polyvinyl alcohol. It had high EE (72.6%), acceptable PS and PDI (362.4 nm and 0.25, respectively) and highly negative ZP of −41.7 mV. OE exhibited higher elasticity than conventional liposomes, with acceptable stability for three months. Transmission electron microscopy demonstrated the spherical morphology of vesicles with an external transparent coat of Hyaluronic acid. OE was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OE for ocular use. The fungal susceptibility testing using
Candida albicans
demonstrated the superiority of OE to VCZ suspension, with greater and more durable growth inhibition. Therefore, OE can be regarded as a promising formula, achieving both safety and efficacy.
“…VCZ-loaded ultradeformable elastosomes were prepared according to a 3 3 Box-Behnken design using Design-Expert® software (Stat-Ease, Inc., Minneapolis, MN) to study the effect of different variables on vesicle properties. It was chosen as it aids in reducing the number of experimental runs needed for conducting the study, hence optimizing costs and saving time (Alruwaili et al., 2020 ; Radwan et al., 2020 ). Factors, their levels and desirability constraints are listed in Table 1 .…”
Voriconazole (VCZ) is a well-known broad spectrum triazole antifungal, mainly used orally and intravenously. The study aimed to formulate VCZ into ultradeformable elastosomes for the topical treatment of ocular fungal keratitis. Different formulae were prepared using a modified ethanol injection method, employing a 3
3
Box-Behnken design. They were characterized by measuring their entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The optimized formula was subjected to further
in vitro
investigations and
in vivo
evaluation studies. The prepared vesicles had satisfactory EE%, PS, PDI and ZP values. The numerical optimization process suggested an optimal elastosomal formula (OE) composed of phosphatidyl choline and brij S100 at the weight ratio of 3.62: 1, 0.25%w/v hyaluronic acid and 5% (percentage from phosphatidyl choline/brij mixture) polyvinyl alcohol. It had high EE (72.6%), acceptable PS and PDI (362.4 nm and 0.25, respectively) and highly negative ZP of −41.7 mV. OE exhibited higher elasticity than conventional liposomes, with acceptable stability for three months. Transmission electron microscopy demonstrated the spherical morphology of vesicles with an external transparent coat of Hyaluronic acid. OE was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OE for ocular use. The fungal susceptibility testing using
Candida albicans
demonstrated the superiority of OE to VCZ suspension, with greater and more durable growth inhibition. Therefore, OE can be regarded as a promising formula, achieving both safety and efficacy.
“… 61 The high viscosity during storage is extremely useful to maintain the physical stability of the dispersed nanovesicles by hindering their aggregation. 62 On the other hand, the gel viscosity will significantly drop-down during application and rubbing which will facilitate spreadability on the skin. 63 , 64 Figure 3 Rheological characteristics of the prepared nanovesicular gel.…”
Purpose
Ivabradine hydrochloride is selective pacemaker current (I
f
) ion channel inhibitor used in case of chronic heart failure (CHF) with superior efficacy and lower side effects than most β-blockers. However, the drug suffers from low bioavailability (≈40%) due to extensive first-pass metabolism. Hence, this work aims to formulate nanovesicular platforms to enhance their bioavailability both orally and transdermally.
Materials and Methods
A central composite face-centered design was employed to formulate the nanovesicles, both phosphatidylcholine: drug ratio and percentage of pluronic F68 were used as independent variables. The nine developed formulae were characterized in terms of vesicle size (nm), polydispersity index, zeta potential (mV), entrapment efficiency (%). Decreasing vesicle size, increasing negative value of the zeta potential, and increasing entrapment efficiency were the chosen constraints to optimize the engineered nanovesicles. The candidate formula was subjected to further investigation including lyophilization, loading into carbopol gel, in vitro release, imaging with a transmission electron microscope, histopathological examination, in vitro cytotoxicity study and in vivo pharmacokinetics.
Results
The optimized nanovesicular formula was composed of lipid: drug ratio of 3.91:1 and 100% pluronic as a stabilizer. It has particle size, zeta potential and entrapment efficiency of 337.6 nm, −40.5 mV and 30.5, respectively. It was then lyophilized in the presence of 5% trehalose as a cryoprotectant, dispersed in 0.5% carbopol to develop the transdermal gel. The two different forms of the candidate formula (lyophilized and gel form) displayed sustained drug release in comparison to drug solution. The histopathological and cytotoxicity studies showed that the optimized formula was safe and highly biocompatible. The pharmacokinetics parameters measured declared a higher C
max
and half-life of both formulae in comparison to market product (Procoralan
®
) with a 2.54- and 1.85-folds increase in bioavailability, respectively.
Conclusion
Hence, the developed nanovesicles can be reported as the first nanoplatforms to be used for simultaneous ivabradine delivery by both oral and topical routes with enhanced oral and transdermal drug delivery. The developed nanoplatforms hence can be further used to formulate other drugs that suffer from low bioavailability due to extensive first-pass metabolism.
“…The results confirmed the synthesized system’s capacity to inhibit both Gram-positive and Gram-negative bacteria growth and biofilm formation [ 114 ]. Alruwaili et al also investigated the antibacterial effects of gentamycin-containing chitosan nanoparticles that were further dispersed into pH-sensitive Carbopol polymer solutions to obtain sol–gel systems ocular delivery [ 115 ]. Ampicillin-loaded chitosan–polyanion nanoparticles were developed by Ciro et al through ionic gelation and polyelectrolyte complexation using anionic polyelectrolytes corresponding to the sodium and potassium salts of poly(maleic acid- alt -ethylene) and poly(maleic acid- alt -octadecene) and studied for their antibacterial properties [ 116 ].…”
Section: Antimicrobial Applications Of Polymeric Nanoparticlesmentioning
Despite the many advancements in the pharmaceutical and medical fields and the development of numerous antimicrobial drugs aimed to suppress and destroy pathogenic microorganisms, infectious diseases still represent a major health threat affecting millions of lives daily. In addition to the limitations of antimicrobial drugs associated with low transportation rate, water solubility, oral bioavailability and stability, inefficient drug targeting, considerable toxicity, and limited patient compliance, the major cause for their inefficiency is the antimicrobial resistance of microorganisms. In this context, the risk of a pre-antibiotic era is a real possibility. For this reason, the research focus has shifted toward the discovery and development of novel and alternative antimicrobial agents that could overcome the challenges associated with conventional drugs. Nanotechnology is a possible alternative, as there is significant evidence of the broad-spectrum antimicrobial activity of nanomaterials and nanoparticles in particular. Moreover, owing to their considerable advantages regarding their efficient cargo dissolving, entrapment, encapsulation, or surface attachment, the possibility of forming antimicrobial groups for specific targeting and destruction, biocompatibility and biodegradability, low toxicity, and synergistic therapy, polymeric nanoparticles have received considerable attention as potential antimicrobial drug delivery agents. In this context, the aim of this paper is to provide an up-to-date overview of the most recent studies investigating polymeric nanoparticles designed for antimicrobial therapies, describing both their targeting strategies and their effects.
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