Development Of Formulations Research Articles

Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 μM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.

Formulation Development of Medicated Chewing Gum by Direct Compression utilizing the SeDeM Diagram Expert System

The main objective of this study was to prepare and characterize the MCG of Ondan HCl which helps to improve the effectivity of the drug and to investigate the applicability of the SeDeM system for the formulation of MCG. The Ondan HCl was formulated into directly compressed MCG utilizing the SeDeM Diagram Expert System. The MCG was optimized using 32 factorial design. Performance evaluation was carried out by evaluating different parameters. Statistical analysis showed that micromeritic properties were improved after inclusion of appropriate excipient in optimum amount. In-vitro drug release study showed 90.01% drug release whereas ex vivo buccal permeation study exhibited significant drug permeation within 15 min indicating its potential for increasing bioavailability. It was concluded that various characteristics of powder material at pre formulation level can be successfully predicted by SeDeM diagram expert system. The developed medicated chewing gum is more effective than mouth dissolving and conventional tablet formulation.
 Keywords: Ondansetron HCl; Medicated chewing gum; direct compression; SeDeM diagram expert system.

A Novel Ex Vivo Blinking Method for Comparing the Corneal Residence Time of New Shampoo Formulations.

In the cosmetics sector, many products such as shampoos have a probability of accidental ocular exposure during their routine use. One very specific safety parameter is the residence time of the substance on the corneal surface, as prolonged exposure may cause injury. In this study, we developed a system that simulates corneal exposure to blinking and tear flow, for comparing the corneal clearance times of viscous detergent formulations. The Ex Vivo Eye Irritation Test (EVEIT), which uses corneal explants from discarded rabbit eyes from an abattoir, was used as the basis for the new system. To simulate blinking, we developed a silicone wiping membrane to regularly move across the corneal surface, under conditions of constant addition and aspiration of fluid, to mimic tear flow. Six shampoo formulations were tested and were shown to differ widely in their corneal clearance time. Three groups could be identified according to the observed clearance times (fast, intermediate and slow); the reference shampoo had the shortest clearance time of all tested formulations. With this new system, it is now possible to investigate an important physicochemical parameter, i.e. corneal clearance time, for the consideration of ocular safety during the development of novel cosmetic formulations.

Unveiling the mechanisms for the development of rosehip-based dermatological products: an updated review

Rosa spp., commonly known as rosehips, are wild plants that have traditionally been employed as herbal remedies for the treatment of a wide range of disorders. Rosehip is a storehouse of vitamins, including A, B complex, C, and E. Among phytonutrients, vitamin C is found in the highest amount. As rosehips contain significant levels of vitamin C, they are perfect candidates for the development of skincare formulations that can be effectively used in the treatment of different skin disorders (i.e., scarring, anti-aging, hyperpigmentation, wrinkles, melasma, and atopic dermatitis). This research focuses on the vitamin C content of several Rosa sp. by their botanical and geographic origins, which according to research studies are in the following order: R. rugosa > R. montana > R. canina > R. dumalis, with lower levels in R. villosa and R. arvensis, respectively. Among rosehip species, R. canina is the most extensively studied species which also displays significant amounts of bioactive compounds, but also antioxidant, and antimicrobial activities (e.g., against Propionibacterium acnes, Staphylococcus aureus, S, epidermis, and S. haemolyticus). The investigation also highlights the use of rosehip extracts and oils to minimise the harmful effects of acne, which primarily affects teenagers in terms of their physical appearance (e.g., scarring, hyperpigmentation, imperfections), as well as their moral character (e.g., low self-confidence, bullying). Additionally, for higher vitamin C content from various rosehip species, the traditional (i.e., infusion, maceration, Soxhlet extraction) and contemporary extraction methods (i.e., supercritical fluid extraction, microwave-assisted, ultrasonic-assisted, and enzyme-assisted extractions) are highlighted, finally choosing the best extraction method for increased bioactive compounds, with emphasis on vitamin C content. Consequently, the current research focuses on assessing the potential of rosehip extracts as medicinal agents against various skin conditions, and the use of rosehip concentrations in skincare formulations (such as toner, serum, lotion, and sunscreen). Up-to-date studies have revealed that rosehip extracts are perfect candidates as topical application products in the form of nanoemulsions. Extensive in vivo studies have revealed that rosehip extracts also exhibit specific activities against multiple skin disorders (i.e., wound healing, collagen synthesis, atopic dermatitis, melasma, and anti-aging effects). Overall, with multiple dermatological actions and efficacies, rosehip extracts and oils are promising agents that require a thorough investigation of their functioning processes to enable their safe use in the skincare industry.

Internal Transcribed Spacers (ITS) Based Identification of Trichoderma Isolates and Biocontrol Activity against Fusarium oxysporum and Chitinase Activity

Twelve Trichoderma spp. isolated from different locations in Uttar Pradesh, India. Internal transcribed spacer (ITS) amplification and sequencing were used to identify isolates of Trichoderma that showed 99–100% identification with Trichoderma harzianum, Trichoderma asperellum, and Trichoderma longibrachiatum, the three species of Trichoderma. Tests were conducted in Vitro to evaluate the biocontrol potential of Trichoderma isolates against Fusarium species. After seven days of incubation, the isolate TBT6 (T. harzianum) exhibited the greatest antagonism against Fusarium oxysporum, with inhibition rates of 87.1%) by TBT7 (82.2%), and the least amount of inhibition (59.7%) by T. longibrachiatum isolate TBT10. Under field conditions, the antagonistic T. harzianum isolate TBT6 can be employed as a bio-control agent against Fusarium oxysporum. and for the development of formulations based on Trichoderma. Using the dual plate approach, twelve highly antagonistic Trichoderma isolates were selected for chitinolytic activity. Observing the breakdown of chitin substrates, Trichoderma isolates TBT6 was shown to have strong chitinolytic enzyme activity, making it a good candidate for endochitinase gene isolation. Using two particular primers, the genomic DNA of the Trichoderma isolate TBT6 was isolated and amplified.

Development of Flame-Retardant Polylactic Acid Formulations for Additive Manufacturing

Polymeric materials, renowned for their lightweight attributes and design adaptability, play a pivotal role in augmenting fuel efficiency and cost-effectiveness in railway vehicle development. The tailored formulation of compounds, specifically designed for additive manufacturing, holds significant promise in expanding the use of these materials. This study centers on poly(lactic acid) (PLA), a natural-based biodegradable polymeric material incorporating diverse halogen-free flame retardants (FRs). Our investigation scrutinizes the printability and fire performance of these formulations, aligning with the European railway standard EN 45545-2. The findings underscore that FR in the condensed phase, including ammonium polyphosphate (APP), expandable graphite (EG), and intumescent systems, exhibit superior fire performance. Notably, FR-inducing hydrolytic degradation, such as aluminum hydroxide (ATH) or EG, reduces polymer molecular weight, significantly impacting PLA’s mechanical performance. Achieving a delicate balance between fire resistance and mechanical properties, formulations with APP as the flame retardant emerge as optimal. This research contributes to understanding the fire performance and printability of 3D-printed PLA compounds, offering vital insights for the rail industry’s adoption of polymeric materials.

Vaccine adjuvants: current status, research and development, licensing, and future opportunities.

Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate immune response and stimulating antigen-presenting cells, leading to a defensive adaptive immune response against a specific pathogen's antigen. As a key element, adjuvants are chemical materials often employed as additives to increase a vaccine's efficacy and immunogenicity. For over 90 years, adjuvants have been essential components in many human vaccines, improving their efficacy by enhancing, modulating, and prolonging the immune response. Here, we provide a timely and comprehensive review of the historical development and the current status of adjuvants, covering their classification, mechanisms of action, and roles in different vaccines. Additionally, we perform systematic analysis of the current licensing processes and highlights notable examples from clinical trials involving vaccine adjuvants. Looking ahead, we anticipate future trends in the field, including the development of new adjuvant formulations, the creation of innovative adjuvants, and their integration into the broader scope of systems vaccinology and vaccine delivery. The article posits that a deeper understanding of biochemistry, materials science, and vaccine immunology is crucial for advancing vaccine technology. Such advancements are expected to lead to the future development of more effective vaccines, capable of combating emerging infectious diseases and enhancing public health.

Development of a Novel Formulation of Bioactive Glass Based Calcium Phosphate Cement for Bone Grafting

AbstractParticulate bone grafting material can travel from the implantation site and diminish the magnitude of required bone formation response and hence its effectiveness. An easily prepared moldable graft that rapidly sets rigid in situ would alleviate this problem and in this study, such an injectable bone graft material is presented. By combining calcium phosphate (CP) salts with a bioactive glass (BG) mixed with a 2.5% Na2HPO4 solution a novel BG‐based calcium phosphate cement (CPC) is produced. Immersion in Tris buffer and simulated body fluid (SBF) solutions result in the rapid generation of octacalcium phosphate (OCP) and hydroxyapatite (HA) phases – a pre‐requisite for “bioactivity”. Cement‐conditioned media does not result in any cytotoxic potential with respect to MTT activity, DNA content, or alkaline phosphatase activity with an osteoblastic cell line. Application of the cement into standardized surgical defects in the minipig mandible results in short‐term, moderate irritation at 3 and 6 weeks and complete replacement of cement with new bone at 12 weeks.

Insights into the Mechanism of Enhanced Dissolution in Solid Crystalline Formulations

Solid dispersions are a promising approach to enhance the dissolution of poorly water-soluble drugs. Solid crystalline formulations show a fast drug dissolution and a high thermodynamic stability. To understand the mechanisms leading to the faster dissolution of solid crystalline formulations, physical mixtures of the poorly soluble drugs celecoxib, naproxen and phenytoin were investigated in the flow through cell (apparatus 4). The effect of drug load, hydrodynamics in the flow through cell and particle size reduction in co-milled physical mixtures were studied. A carrier- and drug-enabled dissolution could be distinguished. Below a certain drug load, the limit of drug load, carrier-enabled dissolution occurred, and above this value, the drug defined the dissolution rate. For a carrier-enabled behavior, the dissolution kinetics can be divided into a first fast phase, a second slow phase and a transition phase in between. This study contributes to the understanding of the dissolution mechanism in solid crystalline formulations and is thereby valuable for the process and formulation development.

Review on: Formulation Development and Evaluation of Transdermal Patch for Inflammation Using Vintex Nirgudi Linn Leaf Extract

Review on: Formulation Development and Evaluation of Transdermal Patch for Inflammation Using Vintex Nirgudi Linn Leaf Extract

Abstract CT058: A multicenter phase 1-2a clinical study of Orotecan (oral irinotecan HCl, VAL-413) in patients with recurrent pediatric solid tumors

Abstract Background: Intravenous irinotecan hydrochloride (IRN-IV) is approved for the treatment of adult colorectal cancer. An off-label regimen of IRN-IV administered as a 60-min i.v. infusion daily for 5-10 days, bi-weekly in combination with other agents such as temozolomide has been recommended for use in treating children with solid tumors (Blaney. ClinCanRes, 2001; Slotkin. PedBloodCan, 2023). While this regimen has shown promise in published clinical trials across a range of pediatric cancers including Ewing sarcoma, neuroblastoma, rhabdomyosarcoma, hepatoblastoma and medulloblastoma, the protracted administration schedule of IRN-IV is costly and inconvenient thereby negatively impacting patients’ quality of life. Oral regimens utilizing IRN-IV have been developed and implemented with favorable tumor responses (Wagner. ClinSarcRes, 2015). Unfortunately, the palatability of the IRN-IV is poor, leading to reduced compliance. Development of an advanced oral formulation to improve tolerability and patient compliance is an important unmet need. VAL-413 is a novel formulation developed to improve the palatability of oral irinotecan. This Phase 1-2a multi-center clinical trial seeks to examine the safety and tolerability of this novel formulation and assess pharmacokinetics compared to the already established oral regimen. This trial is ongoing (CT.gov: NCT04337177) and currently enrolling the 110mg/m2/day cohort, with no dose limiting toxicity observed to date. Initial pharmacokinetic observations demonstrate similarity for the VAL-413 formulation and i.v. irinotecan given orally for both the parent compound and SN38 active metabolite. TABLE 1. NAND Methods Eligibility: Up to 20 patients ≥ 1 year of age or ≤ 30 years of age with recurrent pediatric solid tumors and adequate bone marrow, renal and liver function, for whom irinotecan therapy is a treatment option will be enrolled. Trial Design: Two different dose levels of VAL-413, 90mg/m2/day or 110mg/m2/day are being studied in combination with fixed-dose temozolomide (100mg/m2/day) using a standard 3 + 3 phase I design. In the event a dose of 90 mg/m2/day is not tolerable due to toxicity, a lower dose of 75 mg/m2/day may be implemented. Treatment: During the first cycle of treatment, each patient will receive 4 daily doses of VAL-413 and one daily dose of the intravenous preparation of irinotecan taken orally (IRN-IVPO). During all subsequent cycles, only VAL-413 will be given with temozolomide in 5-day courses administered every 21 days, as tolerated. Outcome Measures: Toxicity is assessed by NCI CCTCAEv5; tumor response is assessed by RECIST 1.1. A taste survey instrument will assess palatability of VAL-413 vs. IRN-IVPO; comparative intrapatient pharmacokinetics of irinotecan and its metabolites is assessed. Citation Format: James Geller, Patrick Thompson, Javier Oesterheld, Aerang Kim, Meghann McManus, Jeffrey Bacha, Dennis M. Brown, Markos Leggas, Sarath Kanekal, Neil Sankar, Lorena Lopez, Noymi Yam, Lars M. Wagner. A multicenter phase 1-2a clinical study of Orotecan (oral irinotecan HCl, VAL-413) in patients with recurrent pediatric solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT058.

Nitrocellulose for Prolonged Permeation of Levofloxacin HCl-Salicylic Acid In Situ Gel.

Currently, the application of solvent exchange-induced in situ gel is underway for drug delivery to the body target site. Nitrocellulose was attempted in this research as the matrix-forming agent in solvent exchange-induced in situ gel for acne and periodontitis treatments. The gel incorporated a combination of 1% w/w levofloxacin HCl and 2% w/w salicylic acid as the active compounds. In order to facilitate formulation development, the study explored the matrix-forming behavior of different concentrations of nitrocellulose in N-methyl pyrrolidone (NMP). Consequently, their physicochemical properties and matrix-forming behavior, as well as antimicrobial and anti-inflammatory activities, were evaluated using the agar cup diffusion method and thermal inhibition of protein denaturation in the egg albumin technique, respectively. All prepared formulations presented as clear solutions with Newtonian flow. Their contact angles on agarose gel were higher than on a glass slide due to matrix formation upon exposure to the aqueous phase of agarose, with an angle of less than 60° indicating good spreadability. Nitrocellulose concentrations exceeding 20% initiated stable opaque matrix formation upon contact with phosphate buffer pH 6.8. The high hardness and remaining force of the transformed gel indicated their robustness after solvent exchange. Fluorescence tracking using sodium fluorescein and Nile red confirmed the retardation of NMP and water diffusion by the nitrocellulose matrix. From the Franz cell permeation study, these drugs could permeate through neonate porcine skin and tissue of porcine buccal from the nitrocellulose in situ forming gel. Their accumulation in these tissues might enable the inhibition of the invading bacterial pathogens. The developed in situ gels effectively inhibited Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, and Porphyromonas gingivalis. Furthermore, the formulations demonstrated an anti-inflammatory effect. The low viscosity of LvSa25Nc makes it appropriate for injectable treatments targeting periodontitis, while the higher viscosity of LvSa40Nc renders it appropriate for topical applications in acne treatment. Therefore, the nitrocellulose in situ gel loaded with combined levofloxacin HCl and salicylic acid emerges as a promising dosage form for treating acne and periodontitis.

Formulation Development of Haritaki Cream by Using 2 (square ) Factorial Design

Creams, in general, are versatile skincare formulations that provide a balance of water and oil to deliver hydration and nutrients to the skin. Eye creams are a category of skincare products specifically designed for the sensitive and delicate skin around the eyes. The skin in this area is thinner and more prone to issues such as fine lines, wrinkles, puffiness, and dark circles. Eye creams are formulated to be lightweight and easily absorbed, and they typically contain ingredients tailored to address these specific concerns. Common ingredients in eye creams include hydrating agents, anti-aging compounds, brightening ingredients, and sometimes caffeine or other ingredients to reduce puffiness. From the developed formulation of haritaki cream we concluded that it can be used for dark circle. It contains various other excipients like potato starch, alovera, methyl and propyl paraben etc. it does not only reduce dark circles but also glows skin and reduces skin damage. As it causes no irritation it is better than allopathic cream. As it had passed all the evaluation parameters like pH, washability, phase separation, irritations, edema, spread ability etc.

Alginate- and Chitosan-Modified Gelatin Hydrogel Microbeads for Delivery of E. coli Phages

Bacterial infections are among the most significant health problems/concerns worldwide. A very critical concern is the rapidly increasing number of antibiotic-resistant bacteria, which requires much more effective countermeasures. As nature’s antibacterial entities, bacteriophages shortly (“phages”) are very important alternatives to antibiotics, having many superior features compared with antibiotics. The development of phage-carrying controlled-release formulations is still challenging due to the need to protect their activities in preparation, storage, and use, as well as the need to create more user-friendly forms by considering their application area/site/conditions. Here, we prepared gelatin hydrogel microbeads by a two-step process. Sodium alginate was included for modification within the initial recipes, and these composite microbeads were further coated with chitosan. Their swelling ratio, average diameters, and Zeta potentials were determined, and degradations in HCl were demonstrated. The target bacteria Escherichia coli (E.coli) and its specific phage (T4) were obtained from bacterial culture collections and propagated. Phages were loaded within the microbeads with a simple method. The phage release characteristics were investigated comparatively and were demonstrated here. High release rates were observed from the gelatin microbeads. It was possible to reduce the phage release rate using sodium alginate in the recipe and chitosan coating. Using these gelatin-based microbeads as phage carrier matrices—especially in lyophilized forms—significantly improved the phage stability even at room temperature. It was concluded that phage release from gelatin hydrogel microbeads could be further controlled by alginate and chitosan modifications and that user-friendly lyophilized phage formulations with a much longer shelf life could be produced.

Folate Receptor-Targeted Nanodelivery of Apigenin in Breast Cancer: Formulation Development, Characterization and In Vitro Evaluation

Cancer is a dreadful disease with a high mortality rate and breast cancer is the most common cancer among females in the world. Different strategies have been used for the treatment of breast cancer, including chemotherapy but it has a wide range of side effects. This problem can be overcome by delivering anticancer agents with nano-formulations. Apigenin (4′,5,7-trihydroxyflavone), present in many different medicinal plants, shows potential anticancer properties in various cancers. However, its use in clinical practice is limited due to its low water solubility and bioavailability. In this study, we examined folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles (PLGA-PEG-FA NPs) containing apigenin for targeted delivery to MCF-7 breast cancer cells. Apigenin-loaded PLGA-PEG and PLGA-PEG-FA NPs were small in size, had a negative zeta potential, showed sustained release of apigenin and showed significantly higher anticancer activity than the free drug in breast cancer cells. The half maximal inhibitory concentration (IC50) values of apigenin, apigenin-loaded PLGA, PLGA-PEG and PLGA-PEG-FA NPs were 50.2, 49.4, 18.1 and 13.3 μM, respectively. Apigenin-loaded PLGA-PEG and PLGA-PEG-FA NPs showed 2.79- and 3.77-fold higher cytotoxicity than the pristine drug. Folate-conjugated PLGA nanoparticles could be developed for potential target-specific delivery of apigenin in the treatment of breast cancer.

Modeling of Styl'One Evolution correction factors for multicomponent mixtures scaling-up to roller compaction

Roll compaction (RC) is a cost-effective dry granulation method, widely implemented in the pharmaceutical industry. In early formulation development however, when the material availability is limited, being able to predict the most important parameters in RC, like gap width and specific compaction force (SCF), to obtain a target ribbon solid fraction (SF) would significantly improve the formulation development efficiency as it would avoid the need of performing experiments on the roller compactor itself. However, at the present state of things, experiments on RC mechanical simulators present an overestimation of the target SF, when compared to roller compactor SF values.Although numerous correction approaches have been developed to improve the predictive performance of different mathematical models applied to the simulation experimental results, no study has collected a database wide enough to demonstrate the validity of a correction factor that allows to accurately simulate the compaction behavior of multicomponent mixtures.Here, 25 different formulations at 40% drug load are compacted at different SCFs, both on a RC mimicking device (Styl'One Evolution) and on an actual roller compactor (Gerteis Mini-Pactor): following a similar approach as Reimer et al. and implementing a simplified version of the Johanson's mathematical model, 4 different correction factors are calculated, depending on how their material properties and pressure dependencies are considered. In conclusion, one correction factor is identified as the optimal trade-off between the SF prediction accuracy on the Gerteis Mini-Pactor and its applicability to a wide range of formulations, as it is independent of the material properties. This finding is particularly relevant when applied to scale-up to this specific roller compactor or early development processes of new formulations that have not been mechanically characterized yet.

Cutaneous targets for topical pain medications in patients with neuropathic pain: individual differential expression of biomarkers supports the need for personalized medicine.

Numerous potential cutaneous targets exist for treating chronic pain with topically applied active pharmaceutical ingredients. This preliminary human skin tissue investigation was undertaken to characterize several key biomarkers in keratinocytes and provide proof-of-principle data to support clinical development of topical compounded formulations for peripheral neuropathic pain syndromes, such as postherpetic neuralgia (PHN). The study intended to identify objective biomarkers in PHN skin on a patient-by-patient personalized medicine platform. The totality of biopsy biomarker data can provide a tissue basis for directing individualized compounded topical preparations to optimize treatment efficacy. Referencing 5 of the most common actives used in topical pain relief formulations (ketamine, gabapentin, clonidine, baclofen, and lidocaine), and 3 well-established cutaneous mediators (ie, neuropeptides, cannabinoids, and vanilloids), comprehensive immunolabeling was used to quantify receptor biomarkers in skin biopsy samples taken from ipsilateral (pain) and contralateral (nonpain) dermatomes of patients with PHN. Epidermal keratinocyte labeling patterns were significantly different among the cohort for each biomarker, consistent with potential mechanisms of action among keratinocytes. Importantly, the total biomarker panel indicates that the enriched PHN cohort contains distinct subgroups. The heterogeneity of the cohort differences may explain studies that have not shown statistical group benefit from topically administered compounded therapies. Rather, the essential need for individual tissue biomarker evaluations is evident, particularly as a means to direct a more accurately targeted topical personalized medicine approach and generate positive clinical results.

Probiotic capacity of commensal lactic acid bacteria from the intestine of Guinea pigs (Cavia porcellus)

The intricate balance of intestinal microbiota is significantly influenced by the pivotal role of indigenous lactic acid bacteria (LAB). These LAB not only contribute to antimicrobial activity and enhance animal health and productivity but also serve as defense against intestinal infections. In the present study, the probiotic potential of LAB strains isolated from various intestinal sections of adult and young guinea pigs (Cavia porcellus) was comprehensively assessed. Strains belonging to the genera Ligilactobacillus, Weissella, Enterococcus, and Limosilactobacillus were also identified. The antibacterial activities of the LAB strains against Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus were quantified. Exopolysaccharide production, adherence capacity, antibiotic resistance, and bile salt tolerance (0.15 %, 0.30 %, and 0.45 %) of LAB were quantified. Further analyses focused on the effects of pH (2.9, 5.0, 6.4, and 7.4), temperature (40, 50, and 60 °C) and NaCl concentrations (3.5 % and 6.5 % w/v) on LAB growth. Strains GCI9 and GDE10 (Ligilactobacillus salivarius), isolated from the cecum and intestine of guinea pigs, exhibited significant antimicrobial activity against S. typhimurium, E. coli and S. aureus. Remarkable adherence capacity to porcine gastric mucin was demonstrated by L. salivarius strains, specifically ACI1, GCI9, and GDE10, with the highest exopolysaccharide levels produced by ACI1 and GCI9 (1.71 and 1.76 mg/mL, respectively). The probiotic potential was further underscored by remarkable bile salt tolerance, especially in strain GDE10, and substantial exopolysaccharide production. These strains displayed notable adaptability to varying environmental conditions, including NaCl concentrations at 3.5 % and 6.5 %, temperatures ranging from 40 to 60 °C, and pH levels of 2.9, 5.0, 6.4, and 7.4. This comprehensive assessment of the probiotic properties of L. salivarius strains, particularly ACI1, GCI9, and GDE10, shows promise for the development of probiotic formulations aimed at enhancing the intestinal health of guinea pigs.

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

Development of nanoliposome formulation of beta-carotene using high speed homogeniser method

Background: Beta carotene has hydrophobic and unstable properties. Nanoliposomes can package various types of drugs, including hydrophilic and hydrophobic drugs, as well as biological substances such as DNA, RNA, and proteins. This allows for more efficient and targeted drug delivery, making it possible to formulate beta-carotene nanoliposomes to improve efficacy and stability. Objective: To formulate and characterise betacarotene liposomes using high speed homogeniser method and to conduct an accelerated stability test on betacarotene liposomes produced using high speed homogeniser method. Methods: Nanoliposomes were prepared by high speed homogeniser method with time variation of 3, 6, 9 and 12 minutes and characterised for particle size, zeta potential value, polydispersity index, encapsulation efficiency, and stability. Results: The preparation of nanoliposomes produced a yellow, odourless suspension with antioxidant activity, with particle size characteristics measuring 200-300 nm, with a polydispersity index of 0.2-0.5 and potential zeta values ranging from -25 mV to -30 mV, encapsulation efficiency value of 97% and morphology of liposome particles in the form of spherical globules with 500x magnification. Conclusion: Formulation with a time variation of 12 minutes has recommended characteristics with spherical shape having good particle size, polydispersity index value, zeta potential value and encapsulation efficiency value.