Nanomedicine: Enhancing Drug Delivery for Effective Pain Management

e-ISSN: 0976-822X, p-ISSN:2961-6042 Available online on http://www.ijcpr.com/ International Journal of Current Pharmaceutical Review and Research 2025; 17(11); 922-937 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 922 Review Article Nanomedicine: Enhancing Drug Delivery for Effective Pain Management Srenwentu Chakraborty1, Divyansh Mathuria2, Chandra Dev Singh3 1Bachelor of Dental Surgery (BDS), Department of Dentistry, K.D. Dental College and Hospital, Mathura, India 2Master of Pharmacy (M.Pharm), Department of Pharmacy, Rajiv Academy for Pharmacy, Mathura, India 3Master of Pharmacy (M.Pharm), Department of Pharmacy, Rajiv Academy for Pharmacy, Mathura, India Received: 01-08-2025 / Revised: 15-09-2025 / Accepted: 21-10-2025 Corresponding author: Dr. Srenwentu Chakraborty Conflict of interest: Nil Abstract Background: The disruptive potential of nanomedicine in pain management is through the use of nanocarriers (liposomes, micelles, polymeric nanoparticles, and emulsions) to improve the improvement in delivery of the drugs that comprise the pain-relieving chemicals. These systems enhance the solubility and stability of drugs they target, and have controlled release, which overcomes the drawbacks of the traditional pain therapies. Methods: This review discusses some nanocarriers used to treat pain specifically; it focuses on their capacity to traverse physiological boundaries such as the blood-brain barrier (BBB). It also discusses how the size and the surface functionalization of nanoparticles affect the distribution of drugs and their therapeutic efficacies. Results: In comparison to the circumstances of the previous administration, nanocarriers have shown increased bioavailability and decreased toxicity as well as delivery of analgesics, especially in neurological and dental pain. They are used in periodontal treatment where drugs are released locally, antibacterial compositions and as supporting implants. Conclusion: Nanomedicine also works by helping to control the pain by delivering drugs to the body with precision and in a sustained manner. Nevertheless, there is a need to investigate other areas of safety in the long run, biodegradability as well as regulatory issues. Additional integration with AI may allow one to be able to treat pain with personalized and efficient approaches. Keywords: Nano Medicine, Drug Delivery, Nano Particle, Targeted Drug Delivery. This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided original work is properly credited. Introduction Acute and chronic pain is one of the primary healthcare burdens, which is commonly being treated with opioids, NSAIDs, and local anesthetics. Nevertheless, the use of such therapeutic methods is constrained by the presence of systemic adverse reactions, tolerance, susceptibility to addiction, and brief action time [1]. The increasing demand of more and safer substitutes has propelled the study of nanomedicine. This review aims to discuss how nanotechnology crossed the boundary in treating pain, especially how engineered nanocarriers enhance drug delivery. Liposomes, polymeric nanoparticles, dendrimers, and mesoporous silica nanoparticles (MSNs) are all nanoparticles that can be optimized in regards to controlled discharge and increased bioaccessibility, as well as site-specific action, even though the blood-tissue boundary (BBB) [2,3]. These characteristics make possible a localized analgesia having less systematic toxicity. On the clinical front, the formulations approved by FDA such as Liposomal bupivacaine (Exparel) and Liposomal morphine (DepoDur tm) have provided long lasting post-operative analgesia up to 72 hours along with decreasing opioid consumption [2]. These benefits are increased by experimental platforms. Indicative of this, MSNs carrying THC - ARA290 or ropivacaine have reported prolonged analgesia in neuropathic and inflammatory pain models [4,5]. On-demand release of drugs delivered by a magnetic electrospun nanofiber could be performed using external magnetic fields, which provides a real-time control on pain relief [6].In spite of the progress, clinical application of long-term safety data and quality control bugs of the biodegradability and immunogenicity, testing procedures have not been standardized yet, and the problems of manufacturing at a larger scale occur [2,3]. The potential and application of smart technology such as biosensing implants, AI-based International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 923 dosing, and so on are still in the initial phase. This review critically evaluates recent progress in nanomedicine for pain management, highlighting novel delivery systems and therapeutic mechanisms. It also identifies major research gaps that must be addressed to transition these technologies from the lab to clinical practice. Nanomedicine for Pain Management Systematic Drug Delivery Using Nanoparticles: Pharmacology and medicine benefit through nano emulsions that function as colloidal dispersion systems of droplets below one micron which separate oil or lipid particles from water.[7] The small size of nano emulsion droplets enhances drug delivery effectiveness so drugs can enter brain cells and cancer cells and other specified targets efficiently.[8] The small size of nano emulsions combined with their penetration capabilities proves highly valuable for brain cancer and neurological disorder treatments because these features let them pass through barriers such as blood-brain barriers.[7] Applied implant devices used for neuro stimulation along with intrathecal drug delivery systems allow targeted medication delivery through specific body areas to give prolonged pain management with reduced side effects. Nano medicine research has transformed pain treatment since it creates improved treatment approaches that establish detailed clinical answers.[9] Nanotechnology innovation serves as an effective force to transform pain management into promising territory. Medical breakthroughs will create personalized drugs that show better outcomes with fewer adverse effects and improved patient healing results. (ref table 1) Systematic Drug Delivery Using Nanogels: Both medical researchers and pharmaceutical scientists actively explore nanogels because of their special attributes and potential in drug delivery systems which belong to the field of nanomedicine.[10] Polymer-based nanogels use their ability to bind high water amounts to create nanometer-scale gel structures. Nanogels provide storage mechanisms for both hydrophilic and hydrophobic medications which release the medications gradually at a controlled rate. The molecular structures of nanogels position them to be useful drugs for diverse therapeutic applications including pain management.[11] Nanogels contain encapsulated NSAIDs or opioids and local anesthetic medications for pain relief through sustained drug release profiles. Therapeutic drug levels remain constant longer which results in fewer medication doses being needed.[12] The controlled drug release capability of nanogels reduces the occurrence of harmful side effects and medicationrelated toxicities. Prolonged pain therapy requires this approach to be effective. (ref table 1) Systematic Drug Delivery Using Nanotubes: The medical community conducts extensive research about nanotubes specifically focused on carbon nanotubes (which experts call CNTs) due to their beneficial properties for multiple clinical applications. The text continues with information about how medical practitioners utilize nanotubes across nanomedicine.[13-14] Therapeutic agents can be encapsulated by singlewalled carbon nanotubes (SWCNTs) because these nanotubes contain internal storage areas that accept drugs. Target drug delivery is achievable through nanotubes because their hollow structure allows precise delivery to specific cellular or tissue locations that delivering both favorable outcomes and reduced adverse effects.[14] Drug release control functionality of nanotubes becomes possible through addition of specific molecules which trigger release at temperature or pH value alterations. (ref table 1) Systematic Drug Delivery Using Nano emulsion: Nano emulsions based on nanotechnology show significant promise across different nano medicine fields. Curved droplets of oil or lipids stabilize into these colloidal suspensions because stabilizing surfactants and co-surfactants keep water and oil (or its opposite) dispersed together.[15] At Index Nano emulsions function effectively in medicine and pharmaceutical work because of their droplet size distribution within 20 to 200 nm range.[20] Nano emulsion systems serve as a valuable tool in cancer therapy because they act as carriers of chemotherapeutic agents toward tumour cells for effective treatment. The drug absorption efficiency of tumor tissue increases when the small droplet size enhances their penetrative ability.[16] Due to their small dimensions nano emulsions can transport through biological boundaries such as the blood-brain barrier so they serve effectively in brain cancer therapy and other diseases that require medication access to inaccessible areas.[17] Nano emulsion therapy enables the simultaneous delivery of cancer drugs with additional agents such as gene therapies or immunotherapies which enhances the effectiveness of cancer treatments.[18] The pharmacological properties of nano emulsions function as vaccine adjuvants when combined with antigens due to their ability to facilitate antigen delivery to immune cells and tissues. The therapeutic potential of vaccines increases along with their effectiveness when dealing with antigens of poor immunogenicity.[19] The incorporation of vaccine antigens in stabilized nano emulsions ensures their stable activity alongside the accomplishment of efficient immune system delivery.(ref table 1,6) International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 924 Table 1: Nanomedicine for Pain Management Nanomedicine Description Examples Nanoparticles Small particles that can carry drugs Liposomes, dendrimers, solid lipid nanoparticles Nanogels Hydrophilic polymer networks Polymeric nanogels Nanotubes Cylindrical structures that can deliver drugs Carbon nanotubes Nanoemulsions Nanoscale droplets Oil-water emulsions Compiled content from following sources: Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacological reports. 2012 Sep 1;64(5):102037. Pinelli F, Ortolà ÓF, Makvandi P, Perale G, Rossi F. In vivo drug delivery applications of nanogels: a review. Nanomedicine. 2020 Nov 1;15(27):270727. Wang Q, Huang JY, Li HQ, Chen Z, Zhao AZ, Wang Y, Zhang KQ, Sun HT, Al-Deyab SS, Lai YK. TiO2 nanotube platforms for smart drug delivery: a review. International journal of nanomedicine. 2016 Sep 21:4819-34. Eqbal A, Ansari VA, Hafeez A, Ahsan F, Imran M, Tanweer S. Recent applications of nanoemulsion based drug delivery system: A review. Research Journal of Pharmacy and Technology. 2021;14(5):2852-8. Figure 1: Flowchart: Types of Nanomedicine for drug delivery Explanation of Pharmacokinetic Modifications: PK of nanomedicine measures the way nanoparticles interact with the body through four steps called absorption, distribution, metabolism and excretion (ADME). Nanomedicines show different pharmacokinetic characteristics than typical drugs because of their dimensions together with their surface characteristics and adjustable release methods.[20,21](ref table 2,3 and graph 1) Table 2: Pharmacokinetic properties of nano medicine Pharmacokinetic Parameter Absorption Distribution Metabolism Excretion Effect of Nanocarriers Increased solubility and permeability Targeted drug delivery to specific tissues Protects drugs from enzymatic degradation Controlled drug clearance Benefit Higher bioavailability Reduced systemic toxicity Prolonged drug action Sustained therapeutic effect Compiled information from: Ravindran S, Suthar JK, Rokade R, Deshpande P, Singh P, Pratinidhi A, Khambadkhar R, Utekar S. Pharmacokinetics, metabolism, distribution and permeability of nanomedicine. Current drug metabolism. 2018 Apr 1; 19(4):327-34. Alalaiwe A. The clinical International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 925 pharmacokinetics impact of medical nanometals on drug delivery system. Nanomedicine: Nanotechnology, Biology and Medicine. 2019 Apr 1; 17:47-61. Pharmacokinetics (PK) of nanomedicine vs. conventional drugs Table 3: PK Parameter Conventional Drug Nanomedicine Absorption Rapid absorption, often limited by solubility Controlled absorption, sometimes via passive or targeted mechanisms Distribution Widely distributed, may cause offtarget effects Enhanced retention in target tissues (e.g., tumors due to EPR effect) Metabolism Rapid metabolism by liver enzymes (CYP450) Reduced metabolism due to protective coatings (PEGylation, liposomes) Excretion Rapid clearance via kidneys/liver Prolonged circulation, sometimes excreted via hepatobiliary route Half-life Short (minutes to a few hours) Long (hours to days) Compiled information from: Ravindran S, Suthar JK, Rokade R, Deshpande P, Singh P, Pratinidhi A, Khambadkhar R, Utekar S. Pharmacokinetics, metabolism, distribution and permeability of nanomedicine. Current drug metabolism. 2018 Apr 1;19(4):327-34. Alalaiwe A. The clinical pharmacokinetics impact of medical nanometals on drug delivery system. Nanomedicine: Nanotechnology, Biology and Medicine. 2019 Apr 1;17:47-61. Figure 2: Pharmacokinetic Parameters: Conventional drug vs. nanomedine International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 926 Figure 3: Pharmacokinetic: Conventional drug vs. nanomedine Role of Nanocarriers in Overcoming the BloodBrain Barrier (BBB): The Blood-Brain Barrier constitutes a highly discriminate protective fence that preserves brain protection from dangerous products yet hinders the entrance of pharmaceutical agents to central nervous system spaces. Nanocarriers present an effective solution to increase drug transport across the BBB for neurological treatment of diseases including Alzheimer’s disease, Parkinson’s disease, brain tumors and chronic pain.[22] (refer table 4 and 5) Table 4: Mechanisms by Which Nanocarriers Overcome the BBB Mechanism Description Nanocarrier Examples Passive Diffusion (Small Lipophilic Nanoparticles) Small, lipid-soluble nanoparticles diffuse through endothelial cells Liposomes, Solid Lipid Nanoparticles (SLNs) Receptor-Mediated Transport (RMT) Nanocarriers mimic natural ligands to bind to BBB receptors and cross via endocytosis Liposomes with transferrin, Dendrimers with lactoferrin Adsorptive-Mediated Transport (AMT) Positively charged nanocarriers interact with negatively charged endothelial cells to cross Cationic Liposomes, Chitosanbased Nanoparticles Nanoparticle-Induced BBB Modulation Some nanoparticles temporarily disrupt tight junctions to enhance drug entry Gold Nanoparticles, UltrasoundActivated Liposomes Compiled information from : Ahlawat J, Guillama Barroso G, Masoudi Asil S, Alvarado M, Armendariz I, Bernal J, Carabaza X, Chavez S, Cruz P, Escalante V, Estorga S. Nanocarriers as potential drug delivery candidates for overcoming the blood–brain barrier: challenges and possibilities. Acs Omega. 2020 Jun 1;5(22):1258395. Types of Nanocarriers Used for BBB Drug Delivery Table 5: Nanocarrier Features Applications Liposomes Biodegradable, lipid-based, customizable Alzheimer's, Brain Tumors Solid Lipid Nanoparticles (SLNs) Lipid-core structure, sustained release Parkinson’s, Neuroinflammation Polymeric Micelles Amphiphilic, high drug-loading capacity CNS Infections, Stroke Therapy Gold Nanoparticles Small size, modifiable surface Drug delivery & BBB opening International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 927 Compiled information from : Ahlawat J, Guillama Barroso G, Masoudi Asil S, Alvarado M, Armendariz I, Bernal J, Carabaza X, Chavez S, Cruz P, Escalante V, Estorga S. Nanocarriers as potential drug delivery candidates for overcoming the blood–brain barrier: challenges and possibilities. Acs Omega. 2020 Jun 1;5(22):12583-95. Figure 4: Comparing different types of nano cariers International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 928 Table 6: Comparing different types of nano cariers Feature Liposome Solid Lipid Nanoparticle (SLN) Micelle Dendrimer Structure Bilayer vesicles made of phospholipids Solid lipid core stabilized by surfactants Amphiphilic molecules forming a core-shell structure Highly branched, tree-like polymeric structure Size Range 50–1000 nm 50–1000 nm 5–100 nm 1–10 nm Composition Phospholipids & cholesterol Solid lipids (triglycerides, fatty acids) Amphiphilic surfactants (lipids, block copolymers) Repetitive polymer units (PAMAM, PPI) Drug Loading Hydrophilic (core), hydrophobic (bilayer) Mostly hydrophobic drugs Hydrophobic drugs (core) Both hydrophilic & hydrophobic drugs Stability Less stable, prone to oxidation More stable than liposomes Stable, but sensitive to dilution Very stable Biocompatibility High High High Moderate to high Controlled Release Moderate Good Good Excellent Surface Modification Possible (PEGylation, ligand attachment) Possible (PEGylation, targeting moieties) Possible (PEGylation) Highly tunable (ligand attachment) Toxicity Low Low to moderate Low Possible cytotoxicity (depends on generation) Applications Drug delivery, gene therapy, vaccines Drug delivery, cosmetics, food, gene therapy Drug delivery, contrast agents Drug delivery, gene therapy, imaging Limitations Short shelf-life, leakage of drugs Limited drug loading, polymorphic transitions Sensitive to dilution, limited cargo Possible cytotoxicity, complex synthesis Compiled information from: Paul S, Pathak H, Sharma HK. An overview on nanocarriers. Nanocarriers for drug-targeting brain tumors. 2022 Jan 1:145-204. Figure 5: Quantitative comparison of Nanocarriers International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 929 Nanoparticles in dental treatments: Scientists first demonstrated nano dentistry with nanoparticles as the foundation to treat dental and oral issues a substantial period ago. The medical field of dentistry underwent a transformation because nanotechnology made possible painless invasive dental operations. Dentistry makes regular use of original anaesthetics (LAs) which include lidocaine, benzocaine together with tetracaine as standard anaesthetic medications. This medicational technique extended analgesic effects and simultaneously lowered the toxic impacts of original anaesthetics through their placement in liposomes, cyclodextrins, lipid nanoparticles, hydrogels, and patches. Nanoliposomes which contain LAs exhibit success as an effective strategy for conducting dental procedures with no associated pain.[24] Figure 6: Nanoparticles in dental treatments Mechanisms of Action of Nanomedicines in Pain Management Targeted Drug Delivery: The application of nanotechnology through targeted drug delivery enables precise medication distribution to specific areas of therapy including cancer cells along with infected tissues and organs in nanomedical practices. The objective of this approach is to increase drug therapeutic efficiency together with reduced effects on normal tissue structures for better patient results.[24] The drug delivery system created by nanomedicine incorporates solid lipid nanoparticles and liposomes and dendrimers and micelles as nanoparticulate and nanosystems to enhance treatment effectiveness. The targeting process enables precise drug delivery regulation because of nanoparticles' small size alongside their high surface area and molecule-facilitated functionalities [25]. The receptor-mediated targeting approach involves adding specific receptor-binding ligands into nanoparticles to enable node-specific interactions when cancer cells and target tissues are overexpressed. The selection process enables targeted cells to take medications inside their structures through receptor-mediated endocytosis. For instance: Antibodies and peptides and small molecules serve as targeting agents on nanoparticles to help specific receptors located on cancer cells including breast cancer cells with the HER2 receptor or ovarian cancer cells with folate receptors. Nanoparticles become functional by adding RGD peptides together with other ligands to direct them towards tumor blood vessel networks. Particular ligands connect with integrins located on tumor blood vessels thus they improve drug delivery to the tumor.[32] ](refer table 7) Sustained Drug Release (refer table 7): Mechanism of action of sustained drug release system are listed below: Diffusion-Controlled Release Mechanism: The controlled delivery system of therapeutic agents from nanocarriers represents sustained drug release which maintains drug concentration at steady levels throughout extended time periods instead of immediate full release. Sustained drug release strategies aim to boost medical treatments by International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Chakraborty et al. International Journal of Current Pharmaceutical Review and Research 930 decreasing dosage requirements and decreasing treatment-related side effects while maintaining therapeutic drug levels throughout extensive time intervals in bloodstream circulation. The control of drug delivery parameters by precise engineering determines the release rate of therapeutic substances from nanocarriers including nanoparticles and nanogels and liposomes and dendrimers thus providing an efficient sustained drug delivery platform. The methods for sustained release from nanocarriers utilize different mechanisms to determine the timing and quantity of drug exit from the carrier system.[26](refer table 7) Matrix-Controlled Release: The embedded drug in a gel or solid matrix gradually dissolves because the matrix breaks down over time. The drug release pattern is governed by the degradation speed of the matrix. When the polymer degrades to non-toxic metabolites the drug becomes available from nanoparticles constructed with biodegradable materials such as poly(lactic-co-glycolic acid) (PLGA). [27] Osmotic-Controlled Release: The drug exits its carrier using osmotic pressure as the controlling factor. Through osmosis water moves into the nanocarrier which leads to drug discharge in a welldefined manner. Podophyllotoxin remains inside osmotically controlled oral delivery systems that automatically initiate drug release through water consumption.[27] Enzyme-Responsive Release: Drugs embedded in nanocarriers will disperse upon exposure to enzymes which break chemical linkages present in the carrier structure. Activating particular enzymes through tissuespecific targeting functions as an advantageous application of this method. Medications reach tumor tissues which overexpress particular enzymes such as matrix metalloproteinases (MMPs) through the use of enzyme-sensitive polymers.[34] Table 7: Mechanisms of Action of Nanomedicines in Pain Management Mechanism Nanomedicine Contribution Example Targeted Drug Delivery Reduces systemic side effects by delivering medications straight to the sites of pain. Liposomes for local drug release Sustained Drug Release Reduces the frequency of administration by regulating the analgesics' rate of release. Nanogels for sustained morphine release Improved Bioavailability Increases the solubility and absorption of medications that are poorly soluble. Nanoparticles carrying hydrophobic drugs Localized Action Reduces adverse effects by concentrating the impact on a particular organ or tissue. Nanoemulsions for targeted delivery to nerve tissues Compiled information from: Sanati M, Afshari AR, Aminyavari S, Kesharwani P, Jamialahmadi T, Sahebkar A. RGD-engineered nanoparticles as an innovative drug delivery system in cancer therapy. Journal of Drug Delivery Science and Technology. 2023 Jun 1; 84:104562. Tan YF, Lao LL, Xiong GM, Venkatraman S. Controlled-release nanotherapeutics: State of translation. Journal of controlled release. 2018 Aug 28; 284:39-48. Betancourt T, Doiron A, Homan KA, BrannonPeppas L. Controlled release and nanotechnology. Nanotechnology in drug delivery. 2009:283-312. Cai W, Song Y, Xie Q, Wang S, Yin D, Wang S, Wang S, Zhang R, Lee M, Duan J, Zhang X. 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