High Drug Entrapment Efficiency Research Articles

Unveiling the potential of ursolic acid modified hyaluronate nanoparticles for combination drug therapy in triple negative breast cancer

Triple negative breast cancer (TNBC) represents the most aggressive and heterogenous disease, and combination therapy holds promising potential. Here, an enzyme-responsive polymeric prodrug with self-assembly properties was synthesized for targeted co-delivery of paclitaxel (PTX) and ursolic acid (UA). Hyaluronic acid (HA) was conjugated with UA, yielding an amphiphilic prodrug with 13.85 mol% UA and a CMC of 32.3 μg/mL. The HA-UA conjugate exhibited ∼14 % and 47 % hydrolysis at pH 7.4 and in tumor cell lysate. HA-UA/PTX NPs exhibited a spherical structure with 173 nm particle size, and 0.15 PDI. The nanoparticles showed high drug loading (11.58 %) and entrapment efficiency (76.87 %) of PTX. Release experiments revealed accelerated drug release (∼78 %) in the presence of hyaluronidase enzyme. Cellular uptake in MDA-MB-231 cells showed enhanced uptake of HA-UA/PTX NPs through CD44 receptor-mediated endocytosis. In vitro, HA-UA/PTX NPs exhibited higher cytotoxicity, apoptosis, and mitochondrial depolarization compared to PTX alone. In vivo, HA-UA/PTX NPs demonstrated improved pharmacokinetic properties, with 2.18, 2.40, and 2.35-fold higher AUC, t1/2, and MRT compared to free PTX. Notably, HA-UA/PTX NPs exhibited superior antitumor efficacy with a 90 % tumor inhibition rate in 4T1 tumor model and low systemic toxicity, showcasing their significant potential as carriers for TNBC combination therapy.

Cryo-Milled β-Glucan Nanoparticles for Oral Drug Delivery.

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a novel nanoparticulate drug delivery system for the oral delivery of gemcitabine to improve its oral bioavailability. In this study, gemcitabine-loaded β-glucan NPs were fabricated using a film-casting method followed by a freezer-milling technique. As a result, the NPs showed a small particle size of 447.6 ± 14.2 nm, and a high drug entrapment efficiency of 64.3 ± 2.1%. By encapsulating gemcitabine into β-glucan NPs, a sustained drug release profile was obtained, and the anomalous diffusion release mechanism was analyzed, indicating that the drug release was governed by diffusion through the NP matrix as well as matrix erosion. The drug-loaded NPs had a greater ex vivo drug permeation through the porcine intestinal epithelial membrane compared to the plain drug solution. Cytotoxicity studies showed a safety profile of the β-glucan polymers, and the IC50s of drug solution and drug-loaded β-glucan NPs were calculated as 228.8 ± 31.2 ng·mL-1 and 306.1 ± 46.3 ng·mL-1, respectively. Additionally, the LD50 of BALB/c nude mice was determined as 204.17 mg/kg in the acute toxicity studies. Notably, pharmacokinetic studies showed that drug-loaded β-glucan NPs could achieve a 7.4-fold longer T1/2 and a 5.1-fold increase in oral bioavailability compared with plain drug solution. Finally, in vivo pharmacodynamic studies showed the promising capability of gemcitabine-loaded β-glucan NPs to inhibit the 4T1 breast tumor growth, with a 3.04- and 1.74-fold reduction compared to the untreated control and drug solution groups, respectively. In conclusion, the presented freezer-milled β-glucan NP system is a suitable drug delivery method for the oral delivery of gemcitabine and demonstrates a promising potential platform for oral chemotherapy.

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia

Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (−19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 μg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 μg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.

FORMULATION AND EVALUATION OF CIPROFLOXACIN MICROSPHERES DESIGNED BY USING NATURAL POLYMERS BY IONIC GELATION TECHNIQUE

Objective: A definitive objective for supporting drug discharge is to expand the remedial movement of the medication while limiting its incidental effects. Microspheres have become a unique medicine delivery mechanism for several disorders in this area. The popular fluoroquinolone antibiotic, Ciprofloxacin, is used to treat a variety of bacterial illnesses. This research aims to create Ciprofloxacin microspheres with sustained drug delivery using natural gum polymers. Methods: To choose and assess the ideal formulation, a variety of formulations (F1–F8) were developed. This work was completed using an innovative technology, the Ionic Gelation method. Central Composite Design (CCD) used the quadratic forward regression approach to carry out the optimization. The evaluation tests include Particle size, Scanning Electron Microscopy (SEM), FTIR, Percentage yield, Drug content, Drug Entrapment effectiveness and in vitro dissolution studies. Results: It was discovered that the best formulation was F4. From optimization, the ANOVA was found to be significant. The uneven, spherical structure of microspheres with a rough outer surface is confirmed by SEM investigation. The absence of drug-polymer interaction is confirmed by the FTIR. The formulation F4 was deemed ideal due to its high drug entrapment efficiency, drug content and maximal drug release (89.25% in 12 h). Conclusion: Due to the least plasma half-life, this drug is designed as microspheres thus maximizing the therapeutic activity and minimizing the negative effects. In this regard, microspheres have emerged as novel drug-delivery systems for various diseases. It maintains effective dose concentration, eliminates night-time dosage and decreases side effects, thus optimizing drug therapy.

Optimization of Lurasidone HCl-Loaded PLGA Nanoparticles for Intramuscular Delivery: Enhanced Bioavailability, Reduced Dosing Frequency, Pharmacokinetics, and Therapeutic Outcomes.

This study aimed to develop a nanoparticle drug delivery system using poly (lactic-co-glycolic acid) (PLGA) for enhancing the therapeutic efficacy of lurasidone hydrochloride (LH) in treatment of schizophrenia through intramuscular injection. LH-loaded PLGA nanoparticles (LH-PNPs) were prepared using the nanoprecipitation technique and their physicochemical characteristics were assessed. Particle size (PS), zeta potential, morphology, % encapsulation efficiency, % drug loading, drug content, and solid-state properties were analyzed. Stability, in vitro release, and in vivo pharmacokinetic studies were conducted to evaluate the therapeutic efficacy of the developed LH-PNPs. The optimized batch of LH-PNPs exhibited a narrow and uniform PS distribution before and after lyophilization, with sizes of 112.7 ± 1.8 nm and 115.0 ± 1.3 nm, respectively, and a low polydispersity index. The PNPs showed high drug entrapment efficiency, drug loading, and drug content uniformity. Solid-state characterization indicated good stability and compatibility, with a nonamorphous state. The drug release profile demonstrated sustained release behavior. Intramuscular administration of LH-PNPs in rats resulted in a significantly prolonged mean residence time compared with the drug suspension. These findings highlight that intramuscular delivery of the LH-PNP formulation is a promising approach for enhancing the therapeutic efficacy of LH in treatment of schizophrenia.

Development of thiolated xanthan gum-stearylamine conjugate based mucoadhesive system for the delivery of biochanin-A to melanoma cells

Recently, instead of creating new active compounds, scientists have been working to increase the bioavailability and residence time of existing drugs by modifying the characteristics of the delivery systems. In the present study, a novel mucoadhesive bioconjugate (SN-XG-SH) was synthesized by functionalizing a polysaccharide xanthan gum (XG) with cysteamine hydrochloride (CYS) and a lipid stearylamine (SN). FTIR, CHNS and 1H NMR studies confirmed the successful synthesis of SN-XG-SH. Mucoadhesion of the thiolated XG was enhanced and evaluated by different methods. Disulfide bond formation between thiolated XG and skin mucus enhances mucoadhesive behavior. The mucoadhesive bioconjugate was used to prepare nanoparticles for the delivery of hydrophobic biochanin-A (Bio-A) for the treatment of melanoma. The thiolated xanthan gum nanoparticles also demonstrated high drug entrapment efficiency, sustained drug release, and high storage stability. The drug loaded nanoparticles (Bio-A@TXNPs) significantly improved the cytotoxicity of Bio-A against human epidermoid cancer cells (A431 cells) by inducing apoptosis and changing mitochondrial membrane potential. In conclusion, thiolation of XG improves its mucoadhesive properties and prolongs the release of Bio-A. Thus, thiolated XG conjugate has a high potential for use as a bioadhesive agent in controlled and localised delivery of drugs in different skin diseases including melanoma.

Synthesis of Quercetin-Loaded Silver Nanoparticles and Assessing Their Anti-Bacterial Potential.

The study delves into the multifaceted potential of quercetin (Qu), a phytoconstituent found in various fruits, vegetables, and medicinal plants, in combination with silver nanoparticles (AgNPs). The research explores the synthesis and characterization of AgNPs loaded with Qu and investigates their pharmaceutical applications, particularly focusing on antibacterial properties. The study meticulously evaluates Qu's identity, and physicochemical properties, reaffirming its suitability for pharmaceutical use. The development of Qu-loaded AgNPs demonstrates their high drug entrapment efficiency, ideal particle characteristics, and controlled drug release kinetics, suggesting enhanced therapeutic efficacy and reduced side effects. Furthermore, the research examines the antibacterial activity of Qu in different solvents, revealing distinct outcomes. Qu, both in methanol and water formulations, exhibits antibacterial activity against Escherichia coli, with the methanol formulation displaying a slightly stronger efficacy. In conclusion, this study successfully synthesizes AgNPs loaded with Qu and highlights their potential as a potent antibacterial formulation. The findings underscore the influence of solvent choice on Qu's antibacterial properties and pave the way for further research and development in drug delivery systems and antimicrobial agents. This innovative approach holds promise for addressing microbial resistance and advancing pharmaceutical formulations for improved therapeutic outcomes.

Preparation of Metformin Biodegradable Polymeric Microparticles by O/O Emulsion Solvent Evaporation: A 32 Full Factorial Design Approach

Background: Sustained release of synthetic polymeric microparticles has gained more attention as drug delivery carriers because of their properties such as good stability, low toxicity, dosing frequency, and simple and mild preparation method. The present work was envisaged to reduce the dosing frequency by preparing drug loaded biodegradable microspheres by the O/O emulsion solvent evaporation technique. Objective: The objective behind microspheres’ preparation is to sustain the metformin release by using ethyl cellulose as a synthetic polymer. The model drug metformin having a low biological half-life (1.5-3 hours) is selected. Methods: As the metformin is highly water soluble in nature, the oil-in-oil solvent evaporation techniques are used and span 80 is utilized as surfactant. The effect of stirring rate and surfactant concentration on the characteristics of encapsulation efficiency and drug release from the microsphere are investigated. Results: The results show that the drug-polymer (1:1) ratio gives better sustained release results. The obtained microparticles are characterized by X-RD analysis and Fe-SEM, and release behavior is checked for release patterns. A 32 full factorial design is employed for the responses. The free-flowing spherical microspheres show high drug entrapment efficiency. Conclusion: The data obtained suggest that microspheres can be successfully designed with sustained release for diabetic treatment.

Biofunctionalization of nanoceria with sperminated hyaluronan enhances drug delivery performance for corneal alkali burn therapy

Corneal alkali burn (AB) injury is the most common sight-threatening injury that is highly associated with oxidative stress, inflammation, apoptosis, angiogenesis, and cell deficiency. Most therapeutic options are ineffective in improving and reversing pathological conditions. This study aims to develop a delivery system based on sperminated hyaluronan (sH)-functionalized nanoceria (Ce-sH nanoparticles (NPs)) with enhanced barrier penetration capability and increased ocular drug bioavailability. The functional surface properties and therapeutic bioactivities of Ce-sH NPs were evaluated. We observed a high tight-junction opening capacity with higher spermine content, resulting in excellent permeability and cellular uptake efficiency (fourfold that of bare Ce NPs). The NPs exhibited high drug (insulin-like growth factor 1, IGF-1) entrapment efficiency (10-fold) and hyaluronidase-triggered controlled slow release (up to 168 h) compared with bare Ce NPs. The IGF-1-loaded Ce-hsH NPs (I@Ce-hsH) had the best wound healing rate (>90 %). In contrast to a clinically used eye drop (dexamethasone), the I@Ce-hsH significantly reduced corneal defects to <1 % and restored the tissue transparency to a normal range within 7 d post-instillation in a rat model of AB. In summary, our bioactive nanoformulations successfully reversed corneal injury and has great potential in the design of biomaterials for ocular therapeutics.

Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: interplay between nuclear factor-kappa β and cathepsin B

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder associated with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (TAN) is a phytomedicine with a documented activity in treating many CNS disorders, particularly PD owing to its unique anti-inflammatory and antioxidant effect. However, its clinical utility is limited by its poor aqueous solubility, short half-life, and hence low concentration reaching targeted cells. This work aimed to develop a biocompatible chitosan-coated nanostructured lipid carriers (CS-NLCs) for effective brain delivery of TAN for PD management. The proposed nanosystem was successfully prepared using a simple melt-emulsification ultra-sonication method, optimized and characterized both in vitro and in vivo in a rotenone-induced PD rat model. The developed TAN-loaded CS-NLCs (CS-TAN-NLCs) showed good colloidal properties (size ≤ 200 nm, PDI ≤ 0.2, and ζ-potential + 20 mV) and high drug entrapment efficiency (> 97%) with sustained release profile for 24 h. Following intranasal administration, CS-TAN-NLCs succeeded to achieve a remarkable antiparkinsonian and antidepressant effect in diseased animals compared to both the uncoated TAN-NLCs and free TAN suspension as evidenced by the conducted behavioral tests and improved histopathological findings. Furthermore, biochemical evaluation of oxidative stress along with inflammatory markers, nuclear factor-kabba β (NF-Kβ) and cathepsin B further confirmed the potential of the CS-TAN-NLCs in enhancing brain delivery and hence the therapeutic effect of TAN of treatment of PD. Accordingly, CS-TAN-NLCs could be addressed as a promising nano-platform for the effective management of PD.Graphical abstract

Doxorubicin layer-by-layer nanoparticles for controlled delivery and effective treatment of pancreatic cancer

Introduction: Layer-by-layer (LbL) nanoparticles consist of a versatile drug delivery technique, for targeted and controlled delivery. The Doxorubicin (DRC) is being widely used for treatment of pancreatic cancer (PCR). The present study was performed to develop and evaluation LbL nanoparticles (NP’s) of DRC to provide controlled and targeted delivery for effective treatment of PCR.&#x0D; Materials and Method: A liposomal based polymeric pH sensitive NP’s were prepared by utilizing LbL techniques. The NP’s were composed lipids, poly (b-amino ester) (PAE) and hyaluronic acid (HAC). The physiochemical properties of DRC-LbL NPs was evaluated such as particle size, zeta potential, percent entrapment efficiency (%EE), loading of drug and In-vitro drug release behavior. The surface morphology of LbL NP’s was evaluated by scanning electronic microscopy (SEM). The in vitro release of DRC-LbL-NP’s was determined by using Dialysis technique at pH 5 and 7.&#x0D; Results: Results showed that developed DRC-LbL NP’s having average particle size of 182.94 + 4.11 nm, zeta potential (ZP) of -42.78± 3.2mV, higher drug entrapment efficiency (EE) of 74.94±3.45. The in-vitro drug release from DRC-LbL NP’s exhibited sustained release pattern and it was triggered by lower pH. The surface morphology of developed DRC-LbL NP’s exhibited smooth and uniform particle size in nano range. The results from in-vitro drug release showed that there was significant difference in amount of DRC release in both pH media. In phosphate buffer pH 7.4 the total amount of DRC release was found to be 44.82 % after 48 hour of study whereas in pH 5.0 it was recorded 98.24% after 48 hours.&#x0D; Conclusion: The results from present study conclude that DRC-LbL NPs might be a promising candidate for the effective treatment of pancreatic cancer.&#x0D; Keywords: Layer-by-layer, Nanoparticles, Doxorubicin, Controlled delivery, Targeted Delivery

Hydrophobic Drug Carrier from Polycaprolactone-b-Poly(Ethylene Glycol) Star-Shaped Polymers Hydrogel Blend as Potential for Wound Healing Application.

Blending hydrogel with an amphiphilic polymer can increase the hydrophobic drug loading and entrapment efficiency of hydrogel-based formulations. In this study, a hydrogel formulation with star-shaped polycaprolactone-b-poly(ethylene glycol) (PCL-b-PEG) as the hydrophobic drug cargo is produced. The 4-arm and 6-arm star-shaped PCL are synthesized with different molecular weights (5000, 10,000, 15,000 g/mol) via ROP and MPEG as the hydrophilic segment is attached via the Steglich esterification. FTIR and 1H-NMR analysis showed the presence of all functional groups for homopolymers and copolymers. Mn for all synthesized polymers is close to the theoretical value while GPC spectra showed a monomodal peak with narrow molecular weight distribution (PDI:1.01-1.25). The thermal degradation temperature and crystalline melting point of synthesized polymers increase with the increase in molecular weight and number of arms. All formulations possess high drug loading and entrapment efficiency (>99%) and increase with increasing molecular weight, number of arms, and amount of polymer in the formulations. All formulations showed a sustained drug release pattern with no initial burst, which follows the Korsmeyer-Peppas kinetic model. The polymer hydrogel formulations showed antibacterial activity against E. coli and S. aureus. The hydrogel containing 4-arm PCL15k-PEG is chosen as the best formulation due to its high drug release, good antimicrobial activity, and morphology.

Nano-Gels: Recent Advancement in Fabrication Methods for Mitigation of Skin Cancer

In the 21st century, melanoma and non-melanoma skin cancers have become an epidemic outbreak worldwide. Therefore, the exploration of all potential preventative and therapeutic measures based on either physical or bio-chemical mechanisms is essential via understanding precise pathophysiological pathways (Mitogen-activated protein kinase, Phosphatidylinositol 3-kinase Pathway, and Notch signaling pathway) and other aspects of such skin malignancies. Nano-gel, a three-dimensional polymeric cross-linked porous hydrogel having a diameter of 20-200 nm, possesses dual properties of both hydrogel and nanoparticle. The capacity of high drug entrapment efficiency with greater thermodynamic stability, remarkable solubilization potential, and swelling behavior of nano-gel becomes a promising candidate as a targeted drug delivery system in the treatment of skin cancer. Nano-gel can be either synthetically or architectonically modified for responding to either internal or external stimuli, including radiation, ultrasound, enzyme, magnetic, pH, temperature, and oxidation-reduction to achieve controlled release of pharmaceuticals and several bio-active molecules such as proteins, peptides, genes via amplifying drug aggregation in the active targeted tissue and reducing adverse pharmacological effects. Several drugs, such as anti-neoplastic biomolecules having short biological half-lives and prompt enzyme degradability capacity, must be appropriate for administration employing either chemically bridged or physically constructed nano-gel frameworks. The comprehensive review summarizes the advancement in the preparation and characterization methods of targeted nano-gel with enhanced pharmacological potential and preserved intracellular safety limits for the mitigation of skin malignancies with a special emphasize on skin cancer inducing pathophysiological pathways and prospective research opportunities for skin malignancy targeted nano-gels.

Optimization of Soya Phosphatidylcholine and Tween 80 As A Preparation of Diclofenac Sodium Transfersome Vesicles Using Design-Expert

Background: Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID) widely prescribed for inflammation and pain. However, when used orally, diclofenac sodium has poor bioavailability because it undergoes first-pass metabolism in the liver, so only about 50% of the drug reaches systemic circulation. Therefore, the transdermal delivery system, in this case, transfersome nanovesicles, was chosen as an alternative to overcome these problems. Transfersome is a lipid vesicle with the best deformability in penetrating the skin layer among other nanovesicles. Transfersomes consist of active substances, phospholipids, surfactants, and other ingredients. The composition of phosphatidylcholine as a phospholipid and tween 80 as a surfactant is a variable that can affect the optimization of the transfersome formula. Therefore, the ratio of phospholipids and surfactants should be varied to obtain the most stable transfersome formula with high drug entrapment efficiency. Optimization as an approach to get the best combination of a formula can be done in a more efficient way using software called Design-Expert. This software is used to help carry out experimental designs, such as determining the optimum formula for a preparation. Objectives: This study aims to determine the ratio of soya phosphatidylcholine as a phospholipid and tween 80 as a surfactant in the optimum formula of diclofenac sodium transfersome vesicles using Design-Expert and to determine the characteristics of the resulting transfersome vesicles. Material and Methods: Optimizing the transfersome Diclofenac Sodium formula using the factorial design 22 with soya phosphatidylcholine and tween 80 factors, particle size response, and entrapment efficiency. The thin layer hydration method carried out the process of making diclofenac sodium transfersome. Results: The results obtained from this study, namely the optimum formula based on Design-Expert, obtained a ratio of soya phosphatidylcholine and tween 80 of 4.5%: 0.5%. The results of the characterization of the optimum formula obtained a particle size of 224.3 nm, a zeta potential of -57.1 mV, and entrapment efficiency of 99.85%. Conclusions: The results of the characterization of the diclofenac sodium transfersome have met the specifications required for each test.

Silk nanoparticles for the protection and delivery of guava leaf (Psidium guajava L.) extract for cosmetic industry, a new approach for an old herb

Guava (Psidium guajava L.) is a well-known plant containing high levels of natural antioxidants, the phenolic compounds, which have been employed in numerous cosmetic products. However, these molecules are unstable to oxidants, light, temperature, pH, water, and enzymatic activities. Therefore, to enhance their stability and preserve their antioxidant activity, this study investigated the silk fibroin nanoparticles (SFNs) ability to encapsulate, deliver, and heat-protect the phenolic compounds of the guava leaves ethanolic extract. Firstly, the guava ethanolic extract was produced by maceration, which possessed a total phenolic content of 312.6 mg GAE/g DPW and a high antioxidant activity (IC50 = 5.397 ± 0.618 µg/mL). Then, the extract loaded SFNs were manufactured by desolvation method, and the particles demonstrated appropriate sizes of 200–700 nm with narrow size distribution, spherical shape, silk-II crystalline structure, high drug entrapment efficiency of > 70% (dependent on the fibroin content), and a two-phase sustained drug release for at least 210 min. Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the antioxidant activity of the guava extract was well-preserved in the extract loaded SFNs. Finally, after being treated with high temperature of 70 °C for 24 h, the guava extract almost loses all of its antioxidant property (5 times decrement), whereas the extract loaded SFNs could retain the extract activity. Conclusively, the SFNs proved much potential to deliver and heat-protect the guava extract phenolic compounds, and preserve their antioxidant activity. Confirmed by this case, SFNs could be further explored in protecting other natural compounds from environmental factors.

Rutin Nanocrystals with Enhanced Anti-Inflammatory Activity: Preparation and Ex Vivo/In Vivo Evaluation in an Inflammatory Rat Model.

Rutin is a polyphenolic flavonoid with an interestingly wide therapeutic spectrum. However, its clinical benefits are limited by its poor aqueous solubility and low bioavailability. In an attempt to overcome these limitations, rutin nanocrystals were prepared using various stabilizers including nonionic surfactants and nonionic polymers. The nanocrystals were evaluated for particle size, zeta potential, drug entrapment efficiency, morphology, colloidal stability, rutin photostability, dissolution rate, and saturation solubility. The selected nanocrystal formulation was dispersed in a hydrogel base and the drug release kinetics and permeability through mouse skin were characterized. Rutin's anti-inflammatory efficacy was studied in a carrageenan-induced rat paw edema model. The nanocrystals had a size in the range of around 270-500 nm and a polydispersity index of around 0.3-0.5. Nanocrystals stabilized by hydroxypropyl beta-cyclodextrin (HP-β-CD) had the smallest particle size, highest drug entrapment efficiency, best colloidal stability, and highest drug photostability. Nanocrystals had around a 102- to 202-fold and 2.3- to 6.7-fold increase in the drug aqueous solubility and dissolution rate, respectively, depending on the type of stabilizer. HP-β-CD nanocrystals hydrogel had a significantly higher percent of drug released and permeated through the mouse skin compared with the free drug hydrogel. The cumulative drug amount permeated through the skin was 2.5-fold higher than that of the free drug hydrogel. In vivo studies showed that HP-β-CD-stabilized rutin nanocrystals hydrogel had significantly higher edema inhibition compared with the free drug hydrogel and commercial diclofenac sodium gel. These results highlight the potential of HP-β-CD-stabilized nanocrystals as a promising approach to enhance drug solubility, dissolution rate, and anti-inflammatory properties.

Sodium Alginate-Quaternary Polymethacrylate Composites: Characterization of Dispersions and Calcium Ion Cross-Linked Gel Beads.

The objective of this work was to examine the effect of quaternary polymethacrylate (QPM), a water-insoluble polymer with a positive charge, on the characteristics of the sodium alginate (SA) dispersions and the calcium alginate (CA) gel beads containing propranolol HCl (PPN). The SA-QPM composite dispersions presented the formation of flocculates with a negative charge due to the electrostatic interaction of both substances. The QPM addition did not affect the SA dispersions' Newtonian flow, but the composite dispersions' viscosity enhancement was found. The PPN-loaded CA-QPM gel beads had more spherical than the PPN-loaded CA gel beads. The incorporation of QPM caused a bigger particle size, higher drug entrapment efficiency, and greater particle strength of the gel beads. Despite the similar water uptake property, the PPN-loaded CA-QPM gel beads displayed lower burst release and slower drug release rate than the PPN-loaded CA gel beads. However, the drug release from the PPN-loaded CA-QPM gel beads involved drug diffusion and matrix swelling mechanisms. This study demonstrated that adding QPM into the SA dispersions leads to a viscosity synergism. The CA-QPM gel beads display a good potential for use as a bioactive compound delivery system.

Levofloxacin in nanostructured lipid carriers: Preformulation and critical process parameters for a highly incorporated formulation

The first step of a successful nanoformulation development is preformulation studies, in which the best excipients, drug-excipient compatibility and interactions can be identified. During the formulation, the critical process parameters and their impact must be studied to establish the stable system with a high drug entrapment efficiency (EE). This work followed these steps to develop nanostructured lipid carriers (NLCs) to deliver the antibiotic levofloxacin (LV). The preformulation studies covered drug solubility in excipients and thorough characterization using thermal analysis, X-ray diffraction and spectroscopy. A design of experiment based on the process parameters identified nanoparticles with < 200 nm in size, polydispersity <= 0.3, zeta potential −21 to −24 mV, high EE formulations (>71 %) and an acceptable level of LV degradation products (0.37–1.13 %). To the best of our knowledge, this is the first time that a drug degradation is reported and studied in work on nanostructured lipids. LV impurities following the NLC production were detected, mainly levofloxacin N-oxide, a degradation product that has no antimicrobial activity and could interfere with LV quantification in spectrophotometric experiments. Also, the achievement of the highest EE in lipid nanoparticles than those described in the literature to date and the apparent protective action of NLC of entrapped-LV against degradation are important findings.

Alpha-Mangostin-Loaded Transferrin-Conjugated Lipid-Polymer Hybrid Nanoparticles: Development and Characterization for Tumor-Targeted Delivery.

Alpha-mangostin, a natural xanthone mainly extracted from the pericarp of Garcinia mangostana, has been shown to have promising anticancer properties in many types of cancer. However, the therapeutic potential of α-mangostin has been limited so far due to its poor aqueous solubility and low oral bioavailability, which limited its biopharmaceutical applications. Furthermore, α-mangostin failed to specifically reach tumors at a therapeutic concentration due and rapid elimination in vivo. We hypothesized that this drawback could be overcome by loading the drug within a delivery system conjugated to transferrin (Tf), whose receptors are overexpressed on many cancer cells and would enhance the specific delivery of α-mangostin to cancer cells, thereby enhancing its therapeutic efficacy. The objectives of this study were therefore to prepare and characterize transferrin-conjugated lipid-polymer hybrid nanoparticles (LPHN) entrapping α-mangostin, as well as to evaluate their therapeutic efficacy in vitro. We successfully prepared α-mangostin loaded LPHN using a one-step nanoprecipitation method with high drug entrapment efficiency. The conjugation of Tf to the LPHN was achieved by using the thiol–maleimide “click” reaction, leading to an increase in the particle hydrodynamic size of Tf-LPHN compared to that of unconjugated (control) LPHN (Ctrl-LPHN). Both Tf-LPHN and Ctrl-LPHN were bearing negative surface charges. Tf-LPHN and Ctrl-LPHN exhibited a sustained release of α-mangostin at pH 7.4, following an initial burst release, unlike rapid release of drug solution. The entrapment of α-mangostin in the LPHN led to an increase in α-mangostin uptake by cancer cells, and thus improved its antiproliferative activity compared to that observed with the drug solution. In conclusion, α-mangostin entrapped in the Tf-LPHN is therefore a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment.

Formulation and evaluation of fusidic acid based transferosome for burn wound infection

Transferosome, being very flexible and deformable nature to cross stratum corneum are selected for enhancing the transdermal delivery of fusidic acid. The present research work comprised formulation of fusidic acid transferosome using modified reverse phase evaporation process and characterised for particle size, zeta potential, entrapment efficiency and in vitro drug release. An optimised formulation of transferosome made by Phosphatidyl choline S100 and Span 80 (F2) showed lowest size of 145.16 nm and high drug entrapment efficiency of 87.47 ± 0.119. 2 %w/v Carbopol based transferosomal gel formulation (N4) of Fusidic acid showed entrapment efficiency 78.22% and Fickian diffusion-based release mechanism with 47% and 94% drug release at 6 h and 24 h respectively. The promising results from the current study can be exploited in future research for in-vivo performance.