Bacterial fermentation offers a sustainable route for producing polyhydroxybutyrate (PHB), a biodegradable polyester synthesized by microorganisms as an energy storage material. Unlike synthetic polyesters derived from petrochemical sources, PHB nanoparticles are biocompatible, exhibit low toxicity, and degrade into non-harmful byproducts, making them ideal for medical and environmental applications. The production process involves microbial cultivation under nutrient-limiting conditions, typically using carbon-rich feedstocks like glucose or agricultural waste. This method significantly reduces reliance on fossil fuels while minimizing carbon emissions.

The crystallinity of PHB plays a critical role in its degradation behavior. PHB nanoparticles with high crystallinity degrade more slowly due to the tightly packed polymer chains that limit water penetration and enzymatic attack. Differential scanning calorimetry (DSC) analysis reveals melting temperatures between 160°C and 180°C, with crystallinity percentages ranging from 60% to 80%, depending on fermentation conditions and post-processing. Thermogravimetric analysis (TGA) demonstrates thermal stability up to 250°C, beyond which decomposition occurs. The degradation rate in physiological environments can be modulated by adjusting the crystallinity through copolymerization or additives, though pure PHB systems are preferred to maintain biodegradability.

Solvent displacement is a widely used method for synthesizing PHB nanoparticles. This technique involves dissolving PHB in an organic solvent such as chloroform or dichloromethane, followed by precipitation into an aqueous phase containing a stabilizer like polyvinyl alcohol (PVA). The rapid solvent diffusion results in nanoparticle formation with sizes typically between 100 nm and 300 nm, as confirmed by dynamic light scattering (DLS). The process avoids high-energy inputs, unlike emulsion-based methods, and yields particles with narrow size distributions suitable for drug delivery.

Compared to synthetic polyesters like polylactic acid (PLA) or polycaprolactone (PCL), PHB exhibits superior biocompatibility but slower degradation rates under ambient conditions. While PLA degrades within months in compost environments, PHB may persist for over a year unless exposed to specific microbial activity. However, in vivo studies indicate that PHB nanoparticles undergo surface erosion, releasing degradation products that are metabolized via the Krebs cycle without inducing inflammatory responses. This property is advantageous for long-term implantable devices or controlled drug release systems.

In sustainable medicine, PHB nanoparticles serve as carriers for hydrophobic drugs, proteins, and nucleic acids. Their lipophilic core efficiently encapsulates therapeutics, while surface modifications with ligands enable targeted delivery. For instance, doxorubicin-loaded PHB nanoparticles have demonstrated enhanced tumor accumulation and reduced systemic toxicity in preclinical models. Additionally, PHB’s piezoelectric properties make it suitable for bone tissue engineering, where electrical stimulation promotes osteogenesis. Scaffolds fabricated from PHB nanofibers support cell adhesion and proliferation without eliciting foreign body reactions.

Environmental benefits further distinguish PHB from conventional plastics. Unlike petroleum-based polymers, PHB degrades fully in marine and soil environments, with studies showing over 90% mass loss within six months under composting conditions. The absence of microplastic accumulation addresses growing concerns about polymer pollution. Moreover, life-cycle assessments indicate that PHB production via bacterial fermentation generates 50% fewer greenhouse gases compared to polyethylene synthesis.

Despite these advantages, challenges remain in scaling PHB nanoparticle production cost-effectively. Fermentation yields are often lower than chemical synthesis routes, and downstream processing requires careful optimization to maintain nanoparticle uniformity. Advances in metabolic engineering, however, are improving bacterial strains for higher PHB productivity, while green solvent alternatives are being explored to reduce environmental impact during nanoparticle fabrication.

The future of PHB nanoparticles lies in expanding their applications while maintaining ecological integrity. Research is ongoing to enhance their functionalization for stimuli-responsive drug delivery and to integrate them into hybrid materials for wound dressings or agricultural coatings. As regulatory frameworks increasingly favor biodegradable alternatives, PHB stands out as a versatile material bridging sustainability and advanced medical technology.

In summary, PHB nanoparticles derived from bacterial fermentation represent a convergence of eco-friendly production and high-performance material science. Their tunable crystallinity, controlled degradation, and biocompatibility position them as a viable alternative to synthetic polyesters in medicine and beyond. With continued innovation in biosynthesis and nanoparticle engineering, PHB-based systems are poised to play a pivotal role in sustainable industrial and biomedical solutions.