Drug Delivery Studies Research Articles

Arterial pharmacokinetics in a patient-specific atherosclerotic artery-a simulation study

Of concern in the paper is a numerical study of endovascular drug delivery in a patient-specific atherosclerotic artery through a mathematical model in which the luminal flow is governed by an incompressible vis- cous Newtonian fluid, and the transport of luminal as well as tissue concentration is modeled as an unsteady convection-diffusion process. An image processing technique has been successfully adopted to detect the edges of the computational domain extracted from an asymmetric (about the centerline of the artery) patient-specific atherosclerotic artery. Considering each pixel as a control volume, the Marker and Cell (MAC) method has been leveraged to get a quantitative insight of the model considered by exploiting physiologically realistic initial, boundary as well as interface conditions. Simulated results reveal that the number as well as the length of separation zone does increase with increasing Re, and the near-wall velocity contour might be important for estimating the near-wall residence time for the pool of drug molecules available for tissue uptake. Results also show that the more the tissue porosity and interface roughness do not necessarily imply the more the effective- ness of delivery, even though they enhance the averaged concentration in the tissue domains, and also the area under concentration diminishes with increasing Peclet number. Thus, the tissue porosity, the Peclet number and various geometrical shapes (interface roughness) play a pivotal role in the dispersion and the effectiveness of drug delivery. GANITJ. Bangladesh Math. Soc.41.1 (2021) 62-77

Optimization of nanovesicular carriers of a poorly soluble drug using factorial design methodology and artificial neural network by applying quality by design approach

The current work aims to utilize a quality by design (QbD) approach to develop and optimize nanovesicular carriers of a hydrophobic drug. Rosuvastatin calcium was used as a model drug, which suffers poor bioavailability. Several tools were used in the risk assessment study as Ishikawa diagrams. The critical process parameters (CPP) were found to be the particle size, polydispersity index, zeta potential, and entrapment efficiency. A factorial design was used in risk analysis, which was complemented with an artificial neural network (ANN); to assure its accuracy. A design space was established, with an optimized nanostructured lipid carrier formula containing 3.2% total lipid content, 0.139% surfactant, and 0.1197 mg % drug. The optimized formula showed a sustained drug release up to 72 h. It successfully lowered each of the total cholesterol, low-density lipoprotein, and triglycerides and elevated the high-density lipoprotein levels, as compared to the standard drug. Thus, the concurrent use of the factorial design with ANN using the QbD approach permitted the exploration of the experimental regions for a successful nanovesicular carrier formulation and could be used as a reference for many nanostructured drug delivery studies during their pharmaceutical development and product manufacturing.

Recent Advances in Fe-MOF Compositions for Biomedical Applications.

To date, number of new and attractive materials have been applied in drug delivery systems (DDDs) to improve the efficiency of the treatment of cancers. Some problems like low stability, toxicity and weak ability of targeting have hampered most of materials for further applications in biomedicine. MIL(MIL = Materials of Institute Lavoisier), as a specific subclass of metal-organic frameworks (MOFs) owns more advantages than other subclass MOFs, such as better biodegradability and lower cytotoxicity. However, until now, systematic -s and analyses of Fe-based MIL on medical applications are rarely though the majority of documents discussed one research branch of the porous materials MOFs. In this review, we have focussed mainly on the latest studies of applications, including bioimaging, biosensing, and antibacterial and drug delivery on Fe-based MIL. The existing shortcomings and future perspectives of the rapidly growing biomedical applications of Fe-based MIL materials addressing dosage and loading strategies issues are also discussed briefly, and further studies with the use of different therapies will be of great interest. This article reviews the Fe-based MOFs design and biomedical application, including biosensing, bioimaging, antibacterial agent, and drug delivery in recent years.

Immunoresponsive Tissue-Engineered Oral Mucosal Equivalents Containing Macrophages.

Macrophages play a key role in orchestrating the host immune response toward invading organisms or non-self molecules in the oral mucosa. Three-dimensional (3D) oral mucosal equivalents (OME) containing oral fibroblasts and keratinocytes are used extensively to mimic the human oral mucosa where they have been employed to examine innate immune responses to both bacterial and fungal pathogens as well as to biomaterials. Although the presence of immune cells is critical in generating an immune response, very few studies have incorporated leukocytes into OME, and to date, none have contained primary human macrophages. In this study, we report the generation of an immunocompetent OME to investigate immune responses toward bacterial challenge. Primary human monocyte-derived macrophages (MDM) were as responsive to bacterial lipopolysaccharide (LPS) challenge when cultured within a 3D hydrogel in terms of proinflammatory cytokine (IL-6, CXCL8, and TNF-α) gene expression and protein secretion compared with culture as two-dimensional monolayers. MDM were incorporated into a type 1 collagen hydrogel along with oral fibroblasts and the apical surface seeded with oral keratinocytes to generate an MDM-containing OME. Full-thickness MDM-OME displayed a stratified squamous epithelium and a fibroblast-populated connective tissue containing CD68-positive MDM that could be readily isolated to a single-cell population for further analysis by collagenase treatment followed by flow cytometry. When stimulated with LPS, MDM-OME responded with increased proinflammatory cytokine secretion, most notably for TNF-α that increased 12-fold when compared with OME alone. Moreover, this proinflammatory response was inhibited by pretreatment with dexamethasone, showing that MDM-OME are also amenable to drug treatment. Dual-labeled immunofluorescence confocal microscopy revealed that MDM were the sole source of TNF-α production within MDM-OME. These data show functional activity of MDM-OME and illustrate their usefulness for investigations aimed at monitoring the immune response of the oral mucosa to pathogens, biomaterials, and for tissue toxicity and anti-inflammatory drug delivery studies.Impact statementThree-dimensional in vitro models of the oral mucosa have been used extensively to investigate the host response to pathogens, but, to date, few have contained primary leukocytes. In this report, we describe the successful incorporation of primary human macrophages into oral mucosal equivalents (OME). These macrophage-containing models were histologically similar to the oral mucosa and immunoresponsive to bacterial lipopolysaccharides by upregulation of key proinflammatory markers. These advanced OME will significantly aid research into host–pathogen interaction, biomaterial toxicity, and drug delivery studies where the presence of an immune cell component is critical to better represent host oral tissue.

Current-Driven Organic Electrochemical Transistors for Monitoring Cell Layer Integrity with Enhanced Sensitivity.

In this progress report an overview is given on the use of the organic electrochemical transistor (OECT) as a biosensor for impedance sensing of cell layers. The transient OECT current can be used to detect changes in the impedance of the cell layer, as shown by Jimison etal. To circumvent the application of a high gate bias and preventing electrolysis of the electrolyte, in case of small impedance variations, an alternative measuring technique based on an OECT in a current-driven configuration is developed. The ion-sensitivity is larger than 1200 mV V-1 dec-1 at low operating voltage. It can be even further enhanced using an OECT based complementary amplifier, which consists of a p-type and an n-type OECT connected in series, as known from digital electronics. The monitoring of cell layer integrity and irreversible disruption of barrier function with the current-driven OECT is demonstrated for an epithelial Caco-2 cell layer, showing the enhanced ion-sensitivity as compared to the standard OECT configuration. As a state-of-the-art application of the current-driven OECT, the in situ monitoring of reversible tight junction modulation under the effect of drug additives, like poly-l-lysine, is discussed. This shows its potential for in vitro and even in vivo toxicological and drug delivery studies.

Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 1. THR-149

Intravitreal (IVT) injection of pharmacological agents is an established and widely used procedure for the treatment of many posterior segment of the eye diseases. IVT injections permit drugs to reach high concentrations in the retina whilst limiting systemic exposure. Beyond the risk of secondary complications such as intraocular infection, the potential of systemic adverse events cannot be neglected. Therefore, a detailed understanding of the rules governing systemic exposure following IVT drug administration remains a prerequisite for the evaluation and development of new pharmacological agents intended for eye delivery. We present here a novel mathematical model to describe and predict circulating drug levels following IVT in the rabbit eye, a species which is widely used for drug delivery, pharmacokinetic, and pharmacodynamic studies. The mathematical expression was derived from a pharmacokinetic model that assumes the existence of a compartment between the vitreous humor compartment itself and the systemic compartment. We show that the model accurately describes circulating levels of THR-149, a plasma kallikrein inhibitor in development for the treatment of diabetic macular edema. We hypothesize that the model based on the rabbit eye has broader relevance to the human eye and can be used to analyze systemic exposure of a variety of drugs delivered in the eye.

Drug delivery and antimicrobial studies of chitosan-alginate based hydroxyapatite bioscaffolds formed by the Casein micelle assisted synthesis

The present study aims to develop a hydroxyapatite (HAP) based scaffold composite for orthopaedic applications and for that, we adopt a Casein (Cs) micelle assisted synthesis route for the formation of a composite. Following the synthesis and characterization of various fluorine (2% and 5%) substituted HAPs (FHAP), they have been tested for the release of Ciprofloxacin (CIP) drug and antimicrobial efficacy. The physicochemical characterization such as FTIR and Raman confirms the successful formation of the HAP composites. Similarly, the powder XRD and FESEM analysis have used for the confirmation of crystallinity and morphological behaviour, respectively. The elemental composition has confirmed using EDX analysis. The antimicrobial studies indicate that the 5% FHAP sample is possessing superior antifungal and antibacterial activities and the highest activity has been observed against the gram-positive bacteria (Staphylococcus aureus) with an inhibition zone of 47 mm while the gram-negative bacteria (Escherichia coli) has only 38 mm inhibition zone. The CIP drug release profile has been controlling with the Cs/5% FHAP sample. Therefore, this composite has carried out for the scaffold formation with the use of chitosan-alginate matrices. Further, characterization of chitosan-alginate/5% FHAP scaffold composite indicates porous, biodegradable, considerable water uptake and retention ability, along with the maintenance of controlled CIP drug-releasing properties. Based on the analysis, the as-synthesized chitosan-alginate/5% FHAP scaffold composite can be suitable for the biomedical and bioengineering applications of bone tissue growth and as an implant.

Synthesis, Characterization, and Nanodisc Formation of Non‐ionic Polymers**

AbstractAlthough lipid nanodiscs are increasingly used in the structural studies of membrane proteins, drug delivery and other applications, the interaction between the nanodisc belt and the protein to be reconstituted is a major limitation. To overcome this limitation and to further broaden the scope of nanodiscs, a family of non‐ionic amphiphilic polymers synthesized by hydrophobic functionalization of fructo‐oligosaccharides/inulin is reported. We show the stability of lipid nanodiscs formed by these polymers against pH and divalent metal ions, and their magnetic‐alignment properties. The reported results also demonstrate that the non‐ionic polymers extract membrane proteins with unprecedented efficiency.

Synthesis, Characterization, and Nanodisc Formation of Non-ionic Polymers*.

Although lipid nanodiscs are increasingly used in the structural studies of membrane proteins, drug delivery and other applications, the interaction between the nanodisc belt and the protein to be reconstituted is a major limitation. To overcome this limitation and to further broaden the scope of nanodiscs, a family of non-ionic amphiphilic polymers synthesized by hydrophobic functionalization of fructo-oligosaccharides/inulin is reported. We show the stability of lipid nanodiscs formed by these polymers against pH and divalent metal ions, and their magnetic-alignment properties. The reported results also demonstrate that the non-ionic polymers extract membrane proteins with unprecedented efficiency.

Ultrasound Triggered Drug Release from Affinity-Based β-Cyclodextrin Polymers for Infection Control.

This work demonstrates a slow, sustained drug delivery system that provides on-demand delivery bursts through the application of pulsed therapeutic ultrasound (TUS). Insoluble β-cyclodextrin-polymer (pCD) disks were loaded with a saturated antibiotic solution of rifampicin (RIF) and used for drug delivery studies. To obtain on-demand release from the implants, TUS was applied at an intensity of 1.8 W/cm2. The therapeutic efficacy of the combination treatment was assessed in bacterial culture via an in vitro Staphylococcus aureus bioluminescence assay. The results demonstrated that the application of pulsed TUS at 3 MHz and 1.8 W/cm2 to pCD implants leads to a significantly higher short-term burst in the drug release rate compared to samples not treated with TUS. The addition of TUS increased the drug release by 100% within 4 days. The pCD disk + RIF stimulated with TUS showed a comparatively higher bacterial eradication with CFU/mL of 4.277E+09, and 8.00E+08 at 1 and 24 h compared with control treated bacteria at 1.48E+10. Overall, these results suggest that the addition of pulsed TUS could be an effective technology to noninvasively expedite antibiotic release on demand at desired intervals.

Spherical versus prolate spheroidal particles in biosciences: Does the shape make a difference?

AbstractIn this mini‐review, the main differences between spherical and spheroidal particles in terms of their size, surface area, morphology, and ability to penetrate biological membranes are described. The main routes of manufacturing of prolate spheroidal particles with controlled aspect ratio are reported. There are also shown exemplary results of computational and experimental studies of spheroids useful in biomedical applications, such as controlled drug delivery and numerical studies of the passage of spheroids through biological membranes. The relations of shape, size, aspect ratio of spheroidal particles and particle–biological membrane interactions, bioavailability, and flow in blood vessels are presented. The perspectives for future studies leading to resolve crucial problems and to explain basic issues related to acting of ellipsoidal particles in biological environment are also discussed.

A Microfluidic Platform for Cavitation-Enhanced Drug Delivery.

An endothelial-lined blood vessel model is obtained in a PDMS (Polydimethylsiloxane) microfluidic system, where vascular endothelial cells are grown under physiological shear stress, allowing -like maturation. This experimental model is employed for enhanced drug delivery studies, aimed at characterising the increase in endothelial permeability upon microbubble-enhanced ultrasound-induced (USMB) cavitation. We developed a multi-step protocol to couple the optical and the acoustic set-ups, thanks to a 3D-printed insonation chamber, provided with direct optical access and a support for the US transducer. Cavitation-induced interendothelial gap opening is then analysed using a customised code that quantifies gap area and the relative statistics. We show that exposure to US in presence of microbubbles significantly increases endothelial permeability and that tissue integrity completely recovers within 45 min upon insonation. This protocol, along with the versatility of the microfluidic platform, allows to quantitatively characterise cavitation-induced events for its potential employment in clinics.

Electrospun meshes of poly (n-butyl cyanoacrylate) and their potential applications for drug delivery and tissue engineering

The aim of the present work was to develop novel meshes of poly (n-butyl cyanoacrylate) (PBCA) nanofibers for potential applications in drug delivery and tissue engineering taking into account the successful application of PBCA in other medical uses. Electrospinning was applied to solutions of PBCA, 103 and 106 Da. 5-fluorouracil was chosen as model drug for the delivery study because of its effectiveness against cancer, while human gingival fibroblasts (HFIB-G) to confirm the biocompatibility of drug-free PBCA meshes and their potential for tissue engineering. PBCA was able to be electrospun in a wide range of molecular weights, producing fibers free of defects with diameters between 380 nm and 6 μm. Meshes of PBCA (105–106 Da) showed high flexibility with Younǵs modulus and maximal tension values in the range of 0.3–1.6 MPa and 0.03–0.13 MPa respectively. Results from the drug delivery study suggested that 5-fluorouracil was homogeneously loaded into PBCA meshes. Its release was extremely slow, initially 20% in 7 days and the rest gradually (until 96 days) in physiological medium at 37 °C. HFIB-G were well attached and proliferated over PBCA nanofibers during 23 days. Results suggested that PBCA meshes serve as excellent frameworks for cell adhesion/proliferation, and for drug delivery extended periods.

A pH-Triggered Polymer Degradation or Drug Delivery System by Light-Mediated Cis/Trans Isomerization of o-Hydroxy Cinnamates.

A new methodology for the pH-triggered degradation of polymers or for the release of drugs under visible light irradiation based on the cyclization of ortho-hydroxy-cinnamates (oHC) to coumarins is described. The key oHC structural motif can be readily incorporated into the rational design of novel photocleavable polymers via click chemistry. This main-chain moiety undergoes a fast photocleavage when irradiated with 455nm light provided that a suitable base is added. A series of polyethylene glycol-alt-ortho-hydroxy cinnamate (polyethylene glycol (PEG)n -alt-oHC)-based polymers are synthesized and the time-dependent visible-light initiated cleavage of the photoactive monomer and polymer is investigated in solution by a variety of spectroscopic and chromatographic techniques. The photo-degradation behavior of the water-soluble poly(PEG2000 -alt-oHC) is investigated within a broad pH range (pH = 2.1-11.8), demonstrating fast degradation at pH 11.8, while the stability of the polymer is greatly enhanced at pH 2.1. Moreover, the neat polymer shows long-term stability under daylight conditions, thus allowing its storage without special precautions. In addition, two water-soluble PEG-based drug-carrier molecules (mPEG2000 -oHC-benzhydrol/phenol) are synthesized and used for drug delivery studies, monitoring the process by UV-vis spectroscopy in an ON/OFF intermittent manner.

Exploring pH dependent delivery of 5-fluorouracil from functionalized multi-walled carbon nanotubes

Multi-walled carbon nanotubes (MWCNTs) can be applied for pH-sensitive delivery of anticancer drugs. Due to the importance of 5-fluorouracil (5-FU) in different tumor therapy regimens, it has been widely used in different pH dependent drug delivery systems. To investigate the pH effects on loading (and release) of 5-FU on (and from) the functionalized MWCNTs and propose the optimum condition for drug delivery, both macroscopic and microscopic studies were carried out using chromatography and molecular dynamic simulation at different conditions. For both levels of studies, different analytical approaches were performed to assess the validity of the methods. The experimental results revealed that 5-FU has more binding affinity to the surface of the nanocarrier at physiological pH (pH = 7.4) and showed more release at acidic conditions (pH = 5.0). Meanwhile it has been observed that basic pH (pH = 9.0) can lead to a dramatic decrease effect on loading of the drug. The results of this study can be used to suggest the optimum pH levels for nanocarbon based formulations of 5-FU in cancer therapy.

Carboxymethylcellulose/polyacrylic acid/starch-modified Fe3O4 interpenetrating magnetic nanocomposite hydrogel beads as pH-sensitive carrier for oral anticancer drug delivery system

Colon cancer is the most usual illness and its oral therapy is an important challenge owing to the serious side effects on the digestive system. For this aim, novel interpenetrating magnetic nanocomposite hydrogel beads were designed based on starch-modified Fe3O4 NPs (St-Fe3O4). Carboxymethylcellulose/polyacrylic acid/starch-modified Fe3O4(CMC/PAA/St-Fe3O4) beads were prepared via a simple method. The prepared materials were fully characterized using different analyses. Anticancer doxorubicin hydrochloride (DOX) and 5-fluorouracil (5-FU) were individually loaded into the prepared nanocomposites by immersing in the solution of drugs to investigate their productivity as the loading of different anticancer drugs. In-vitro drug delivery study was performed in mimicking the gastrointestinal tract (GIT) circumstances to demonstrate the efficiency of the prepared carrier as an oral delivery system (ODS). The drug release study revealed that CMC/PAA/St-Fe3O4 nanocomposites could potentially prevent the release of 5-FU and DOX in the stomach acidic environment due to their pH-sensitive swelling manner, and also enhance the stability of drug dosing in the colorectal area. MTT assay showed significant cytotoxicity toward human colon cancer cell lines (SW480) for the drug-loaded nanocomposites; thus, they could potentially be administrated as an efficient carrier for anticancer ODS.

Bioscaffold-based study of glioblastoma cell behavior and drug delivery for tumor therapy

Glioblastoma multiforme (GBM) is a severe form of brain cancer with an average five-year survival rate of 6.7%. Current treatment strategies include surgical resection of the tumor area and lining the lesion site with therapeutics, which offer only a moderate impact on increasing survival rates. Drug-testing models based on the monolayer cell culture method may partially explain the lack of advancement in effective GBM treatment, because this model is limited in its ability to show heterogeneous cell-cell and cell-environment interactions as tumor cells in the in vivo state. The development of bioscaffold-based culture models is an important improvement in GBM research, preclinical trials, and targeted drug testing, through better mimicking of the heterogeneity of tumor environmental conditions. A major hurdle towards better GBM outcomes is in delivering medication across the blood-brain barrier (BBB), which normally prevents the crossing of materials into the treatment site. The delivery of therapeutics using bioscaffolds is a potential means of overcoming the BBB and could potentially facilitate long-lasting drug release. A number of natural and synthetic materials have been studied for their biodegradability, toxicity, distribution, and pharmaceutical stability, which are needed to determine the overall effectiveness and safety of glioblastoma treatment. This review summarizes advancements in the research of bioscaffold-based GBM cell growth systems and the potential of using bioscaffolds as a carrier for drug delivery.

Bibliometric Analysis of Global Research Trends on Ultrasound Microbubble: A Quickly Developing Field.

Background: Microbubbles are widely used as highly effective contrast agents to improve the diagnostic capability of ultrasound imaging. Mounting evidence suggests that ultrasound coupled with microbubbles has promising therapeutic applications in cancer, cardiovascular, and neurological disorders by acting as gene or drug carriers. The aim of this study was to identify the scientific output and activity related to ultrasound microbubble through bibliometric approaches. Methods: The literature related to ultrasound microbubble published between 1998 and 2019 was identified and selected from the Science Citation Index Expanded of Web of Science Core Collection on February 21, 2021. The Scopus database was also searched to validate the results and provided as supplementary material. Quantitative variables including number of publications and citations, H-index, and journal citation reports were analyzed by using Microsoft Excel 2019 and GraphPad Prism 8.0 software. VOS viewer and CiteSpace V were used to perform coauthorship, citation, co-citation, and co-occurrence analysis for countries/regions, institutions, authors, and keywords. Results: A total of 6088 publications from the WoSCC were included. The United States has made the largest contribution in this field, with the majority of publications (2090, 34.3%), citations (90,741, 46.6%), the highest H-index (138), and close collaborations with China and Canada. The most contributive institution was the University of Toronto. Professors De Jong N and Dayton P A have made great achievements in this field. However, the research cooperation between institutions and authors was relatively weak. All the studies could be divided into four clusters: “ultrasound diagnosis study,” “microbubbles’ characteristics study,” “gene therapy study,” and “drug delivery study.” The average appearing years (AAY) of keywords in the cluster “drug delivery study” was more recent than other clusters. For promising hot spots, “doxorubicin” showed a relatively latest AAY of 2015.49, followed by “nanoparticles” and “breast cancer.” Conclusion: There has been an increasing amount of scientific output on ultrasound microbubble according to the global trends, and the United States is staying ahead in this field. Collaboration between research teams still needs to be strengthened. The focus gradually shifts from “ultrasound diagnosis study” to “drug delivery study.” It is recommended to pay attention to the latest hot spots, such as “doxorubicin,” “nanoparticles,” and “breast cancer.”

Addressing the Exigent Role of a Coumarin Fluorophore toward Finding the Suitable Microenvironment of Biomimicking and Biomolecular Systems: Steering to Project the Drug Designing and Drug Delivery Study.

The photophysics of 4-azidocoumarin (4-AC), a novel fluorescent coumarin derivative, is well established by the investigation of the alteration of the microheterogeneous environment comprising two types of systems: supramolecular systems, cyclodextrins (CDs), and biomolecular systems, serum albumins (SAs). The enhanced emission of the ligand with the organized assemblies like α-CD, β-CD, and γ-CD by steady-state and time-resolved fluorescence and fluorescence anisotropy at 298 K is compared with those of bovine serum albumin (BSA) and human serum albumin (HSA). The remarkable enhancement of the emission of ligand 4-AC along with the blue shift of the emission for both the systems are visualized as the incorporation of 4-AC into the hydrophobic core of the CDs and proteins mainly due to reduction of nonradiative decay process in the hydrophobic interior of CDs and SAs. The binding constants at 298 K and the single binding site are estimated using enhanced emission and anisotropy of the bound ligand in both the systems. The marked enhancement of the fluorescence anisotropy indicates that the ligand molecule experiences a motionally constrained environment within the CDs and SAs. Rotational correlation time (θc) of the bound ligand 4-AC is calculated in both the categories of the confined environment using time-resolved anisotropy at 298 K. Molecular docking studies for both the variety of complexes of the ligand throw light to assess the location of the ligand and the microenvironment around the ligand in the ligand–CD and ligand–protein complexes. Solvent variation study of the probe 4-AC molecule in different polar protic and aprotic solvents clearly demonstrates the polarity and hydrogen-bonding ability of the solvents, which supports the alteration of the microenvironments around 4-AC due to binding with the biomimicking as well as biomolecular systems. Dynamic light scattering is employed to determine the hydrodynamic diameter of free BSA/HSA and complexes of BSA/HSA with the ligand 4-AC.

Green Formulation of Microbial Biopolyesteric Nanocarriers Toward In Vitro Drug Delivery and Its Characterization

In the present study, formulation and characterization of microbial biopolyesteric nanocarrier (MBPNc) was reported for in vitro controlled release of the drugs, viz., amoxicillin and levofloxacin. The synthesis of microbial biopolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticle was done by a triple emulsion method and loaded with amoxicillin and levofloxacin to improve its curative bioavailability. The synthesized MBPNc was found to be spherical in shape with a size range of 50-100nm which was confirmed through Transmission Electron Microscopy (TEM) analysis. The surface topology and physicochemical characteristics were analyzed by Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR), and X-Ray Diffraction (XRD) spectroscopy. The cell viability % of MBPNc, amoxicillin-loaded MBPNc, and levofloxacin-loaded MBPNc on HEK293 cells at a concentration of 400µg/ml were found to be 93.43 ± 0.66%, 92.29 ± 0.61%, and 91.53 ± 0.46%, respectively, which confirmed that MBPNc is biocompatible and can be used for biomedical applications without any cytotoxic effect. A significant decrease in the bacterial survival ratio (%) and increase in the zone of inhibition were observed on increasing the concentration of drug-loaded MBPNc against E. coli (ATCC®8739™) and S. aureus (ATCC®23,235™). The in vitro drug delivery study showed controlled release of amoxicillin (99.85 ± 0.15%) and levofloxacin (99.73 ± 0.24%) up to 22h.